Murgan S , Castro Colabianchi AM , Monti RJ , Boyadjián López LE , Aguirre CE , Stivala EG , Carrasco AE , López SL .

	FIGURE 1: FoxA4 depletion altered the expression of mesodermal markers, impaired axis elongation, expanded the prechordal mesoderm and reduced the notochord. (A–J) Expression of mesodermal markers at stage 13, dorsal views. (A, F) myod. (B, G) bra. (C, H) gsc. (D, I) frzb1. (E, J) chd. Embryos were injected into one dorsal cell at the 4-cell stage with 40 ng of CtrlMO (A) or of FoxA4MO (B), or with 20 ng of each MO into both dorsal cells at the 4-cell stage, (CtrlMO: B,C,E; FoxA4MO: G, H, J) or at the 1-cell stage (CtrlMO: D; FoxA4MO: I). The myoD domain was shortened on the injected side (is) by FoxA4MO (58%, n = 12) (F). The bra domain was split by FoxA4MO (G) (79%, n = 24). The gsc domain was posteriorly expanded by FoxA4MO (100%, n = 15) (H). The frzb1 domain was posteriorly expanded by FoxA4MO (100%, n = 14) (I). The chd domain was affected in 100% of the injected embryos (n = 14) (J). Among these, 71% showed an expansion of the anterior chd domain, corresponding to the PM (green arrow), while the posterior domain (corresponding to the notochord) was severely reduced (red arrow). In the remaining 29%, the entire axial mesoderm appeared much thinner and shorter than in CtrlMO-injected siblings (inset in J). Similar results were obtained after injection of 20 ng of FoxA4MO into 1-cell stage embryos (Fig. S1B). (K) The body length between the cement gland and the tip of the tailbud was measured at tailbud stage in embryos injected before the first cleavage with 20 ng of CtrlMO (green bar, n = 25) or of FoxA4MO (red bar, n = 27). P<0.0001, two-tailed t-test. (L) Notochord/embryo length ratio measured in the group of embryos corresponding to those shown in (B, G). Green bar, CtrlMO (n = 18); red bar, FoxA4MO (n = 24). P<0.0001, two-tailed t-test. (M–R) Expression of axial mesodermal markers at stage 10.25. (M, P) gsc. (N, Q) frzb1. (O, R) chd. Embryos were injected with 20 ng of CtrlMO (M–O) or of FoxA4MO (P–R). Injections were performed unilaterally in 1 cell at the 2 or 4-cell stage or at the 1-cell stage, giving similar results. Unilateral injections are shown here. The injected side was identified by DOG fluorescence and is oriented to the right (insets in M–R). In gastrulae, we were able to observe an expansion of gsc (58%, n = 40; P) and of frzb1 domains (88%, n = 33; Q). chd expression was reduced in the less involuted, superficial cells on the injected side (red arrows), but a cloud of deep cells expressing chd persisted (green arrows), and even appeared to be expanded on the injected side in some embryos, like the one shown below (50%, n = 10) (R). doi:10.1371/journal.pone.0110559.g001
	Figure 2. FoxA4MO disrupted DML formation. (A–H) Stage 15 embryos left uninjected (A) or injected with 0.5 ng of foxA4FL mRNA (E), 40 ng of CtrlMO (B–D) or of FoxA4MO (F–H) before the first cleavage. (I–T) Tailbud stage embryos injected into two dorsal cells at the 4-cell stage with 20 ng of CtrlMO or of FoxA4MO. The descendants of these cells give rise to the DML and the cephalic region. Expression of chd (A, B, E, F, I, J, M, N, Q, R), shh (C, G, K, L, O, P, S, T), hairy2 (D, H). The inset in K shows a magnified view of the area depicted by the rectangle; fp, floor plate; no, notochord; h, hypochord. Embyos injected with foxA4FL mRNA showed a thicker notochord than control siblings, as revealed by chd expression (87%, n = 15) (E). The percentage of embryos injected with FoxA4MO showing the indicated changes in the corresponding markers is indicated between parentheses, as follows. At neural plate stage, the expression of chd (90%, n = 20) (F) and shh (54%, n = 22) (G) was patchy, and hairy2 expression was reduced in the FP domain (60%, n = 23) (H). At stage 26, the chd domain was patchy and/or thinner (80%, n = 21) (M, N, Q, R). Arrowheads point to chd + cells in dorsal and ventral positions with respect to a notochordal gap. Shh was also patchy (arrowheads, O, P) or completely abolished (S,T) (86%, n = 22). In overall, tailbuds injected with FoxA4MO showed reduced heads (89%, n = 51) (M, Q, O, S). (A–H, J, L, N, P, R, T) dorsal views; (I, K, M, O, Q, S) lateral views. doi:10.1371/journal.pone.0110559.g002
	Figure 3. The DML is invaded by paraxial mesoderm and neuroectoderm in FoxA4 morphants. Dorsal views of embryos at neural plate stage hybridised with myf5 (A, D), myoD (B, E, G, H), or sox2 probes (C, F). They were injected before the first cleavage with 20 ng CtrlMO (A–C) or of FoxA4MO (D–F), 0.25 ng of foxA4FL mRNA (H), or left uninjected (G). In FoxA4 morphants, myf5 (D) and myoD expression (E) was found in the DML (40%, n = 23; 56%, n = 23, respectively). The left embryo in E shows that myoD expression invaded the DML along the A–P axis. The right embryo in E shows stretches of the myoD domains fused at the midline (arrowheads). Sox2 transcripts obliterated the prospective FP (79%, n = 19) (F). In embryos injected with foxA4FL mRNA, myoD expression was reduced, and the medial borders of the bilateral domains were more separated (H, 42%, n = 26) than in control siblings (G). doi:10.1371/journal.pone.0110559.g003
	Figure 4. Knock-down and overexpression of foxA4 shifted the anterior boundary of sox2 in opposite directions. Sox2 expression in stage 14–15 embryos injected with 20 ng of CtrlMO (A, E) or FoxA4MO (B, F) or with 0.5 ng of foxA4FL mRNA (D, H) into one cell at the 2 cell stage, or left uninjected (C, G). FoxA4MO produced a caudal shift (62,5%, n = 16) (B, F). FoxA4FL mRNA produced an anterior shift of the anterior boundary of sox2 (52%, n = 23) (D, H). (A–D) dorsal views; (E–H) anterior views; is, injected side; nis, non-injected side. doi:10.1371/journal.pone.0110559.g004
	Figure 5. Xanf1 and otx2 progressively establish complementary domains. Normal expression of Xanf1, en2 and hoxb7 (A, B, C) and otx2 and krox20 (D–F) in progressively older neural plate stage embryos in anterior views. Yellow asterisks, posterior border of Xanf1 in the ANR; red asterisks, anterior border of Xanf1 in the ANR; white asterisks, SHA; black asterisks, expression hole in the neural otx2 subdomain; black arrows, caudal diencephalic-mesencephalic stripes demarcating the posterior border of the otx2 neural subdomain; yellow arrows, stripe corresponding to the anterior border of otx2 in the ANR; red arrows, SHA; white arrows, CGA. (G) Diagram summarising the expression patterns of otx2, Xanf1, en2, and krox20 in an anterior view of embryos at the stages shown in B, C, E, F. ANR, anterior neural ridge; r3, third rhombomere; m/h, midbrain/hindbrain boundary. doi:10.1371/journal.pone.0110559.g005
	Figure 6. FoxA4 overexpression produced complementary effects on Xanf1 and otx2 and disfavoured anterior development. (A, B, F, G, K, L) Anterior views of early neural plate stage embryos analysed by WMISH with the following markers: Xanf1 and en2 (A, F, K), otx2 and krox20 (B, G, L). Embryos were injected with 0.25 ng (F, K) or 1 ng (G, L) of foxA4FL mRNA before the first cleavage, or were left uninjected (A, B). FoxA4 overexpression affected Xanf1 expression in 83% of the injected embryos (n = 23) as follows: it was reduced in the ANR but not in the SHA (48%, n = 23) (F), or it was reduced in the whole domain (35%, n = 23) (K). The expression hole of the otx2 domain was filled with otx2 transcripts (42%, n = 19) (G); the otx2 domain was reduced, but the caudal diencephalic/mesencephalic stripes were expanded (89%, n = 19) (L). (C–E, H–J, M–O) Anterior views of tailbuds (stage 27/28) injected with 0.25 ng (H, I, M, N) or 0.5 ng (J, O) of foxA4FL mRNA before the first cleavage (I, J, M–O) or into one cell at the 2-cell stage (H), or left uninjected (C, D, E). Expression of otx2 (C,H,M), Xanf1 and en2 (D, I, N), Xag1/N-tubulin (E, J, O). After overexpression of foxA4, the caudal diencephalic otx2 subdomain was expanded anteriorly (54%, n = 13) (H) or the telencephalic otx2 subdomain disappeared (40% n = 10) (M). The pituitary Xanf1 domain was expanded (33%, n = 15) (I). N-tubulin expression in the rostral forebrain (rectangle in E) was deleted and the Xag1 + cement and hatching glands were reduced (J) or the cement gland was absent (O) (54%, n = 24). The most severe phenotypes presented head truncations (23%, n = 13) (M,N,O). Red arrowhead, anterior limit of the caudal diencephalic otx2 subdomain; white arrowhead, posterior limit of the ventral telencephalic otx2 subdomain; vtel, ventral telencephalic otx2; cdi, caudal diencephalic otx2; mes, mesencephalic otx2; op, olfactory placode; epiph, epiphisis; ev, eye vesicle; cg, cement gland; hg, hatching gland cells; pit, pituitary anlage; is, injected side; nis, non-injected side. doi:10.1371/journal.pone.0110559.g006
	Figure 7. FoxA4 inhibition affected anterior ectodermal/neural specification. Embryos at early neural plate stage injected with 20 ng of CtrlMO or of FoxA4MO before the first cleavage (A, B, F, G, K–N, P–S) or unilaterally injected into 1 cell at the 2-cell stage (C, D, H, I, O, T). The injected side was determined by DOG fluorescence (insets). Embryos were hybridised with the following probes: Xanf1, en2, and hoxb7 (A–C, F–H); hoxc6 (D, I); otx2 and krox20 (K, L, P, Q); Xag1 and N-tubulin (M, N, R, S); en2 and hoxb1 (O, T). Green arrows in (A, F) point to the anterior limit of hoxb7. At neural plate stage, Xag1 marks the cement gland anlage (indicated between red arrowheads in N), and the hatching gland primordia (red arrows in N) [98] [90]. Black arrowhead in (H), caudal shift of Xanf1 and fusion with the en2 stripe. Black arrow in (H), fusion of the SHA and the ANR. Red arrow in (I), down-regulation of hoxc6 on the injected side. Yellow arrowhead in (Q), diffuse CGA and anterior border of the ANR. Notice the down-regulation and the caudal shift of en2 (red arrows) and hoxb1 (green arrows) by comparing the injected side (right) with the non-injected side (left) in the FoxA4 morphant in (T) and with the CtrlMO-injected embryo in (O). (E) Ratio between the distance from the posterior limit of Xanf1 to the blastopore and the total length of the embryo in the groups shown in A, B, F, G (r-Xanf1). The ratio was significantly lower in FoxA4 morphants; P<0.0001, two-tailed t-test. (J) The ratio between the length of the hoxb7 domain and the embryo’s length was significantly lower in FoxA4 morphants, as measured in the groups shown in A, B, F, G; P<0.0001, two-tailed t-test. ANR, anterior neural ridge; CGA, cement gland anlage; SHA, stomodeal-adenohypophyseal anlage; m/h, midbrain/hindbrain boundary; m, d, presumptive mesencephalic and caudal diencephalic regions expressing otx2; r3, third rhombomere; r4, fourth rhombomere. (A, D, F, I, K, M, O, P, Q, R, T) are dorsal views; (B, C, G, H, L, N, Q, S) are anterior views. doi:10.1371/journal.pone.0110559.g007
	Figure 8. Depletion of FoxA4 led to head defects at tailbud stages. Anterior views of stage 27/28 embryos injected with 20 ng of CtrlMO (A–E) or FoxA4MO (G–K). Embryos were injected into one dorsal cell at 4-cell stage (A, G) or prior to the first cleavage (B–E, H–K). Expression of otx2 (A, B, G, H), six3 (C, I), emx1 (D, J) and Xanf1 (E, K). Results are summarised in F, L. In embryos unilaterally injected with FoxA4MO, the telencephalic and caudal diencephalic otx2 subdomains were fused in the injected side (red arrowhead), and the eye was lost (70%, n = 24) (G). When FoxA4MO was homogenously distributed, the otx2 domain was reduced, the telencephalic subdomain was fused in the midline and also, with the caudal diencephalic subdomain (80%, n = 20) (H). FoxA4MO reduced the expression domains of six3 (87%, n = 23) (I), emx1 (80%, n = 26) (J) and Xanf1 (70%, n = 20) (K). dtel, dorsal telencephalon; vtel, ventral telencephalic otx2; cdi, caudal diencephalic otx2; mes, mesencephalic otx2; op, olfactory placode; epiph, epiphisis; ev, eye vesicle; cg, cement gland; pit, pituitary anlage; is, injected side; nis, non-injected side. The black line in F, L represents the contour of the head. For comparison, the head contour of the CtrlMO-injected embryo was projected on the FoxA4 morphant diagram (dotted black line in L). doi:10.1371/journal.pone.0110559.g008
	Figure 9. FoxA4 depletion altered neurogenesis along the A–P axis. (A–J) N-tubulin and Xag1 expression in stage 27/28 embryos injected with 40 ng of CtrlMO (A, C, E–G) or FoxA4MO (B, D, H–J) into one cell at the 2-cell stage. (A, B) Dorsal views. (C, D) Magnified images of the trunk region of another pair of CtrlMO (C) and FoxA4MO (D) injected embryos, shown in dorso-lateral views to facilitate comparisons. The red arrow points to an N-tubulin + projection on the injected side. (E, F, H, I) Lateral views of the head region. (G, J) Anterior views. N-tubulin is expressed in the trigeminal (tn) and vestibulocochlear (vn) nerves. In FoxA4MO-injected embryos, the tn and vn were disturbed (red arrowhead) (H), as revealed by N-tubulin; the cement gland (cg) was bent and closer to the forebrain, and the hatching gland (hg) was shortened on the FoxA4-depleted side, as revealed by Xag1 (green arrowhead) (J) (90%, n = 21). (K–N) Transverse sections at the levels indicated by dotted black lines in C,D, shown in bright field (K, M) and their corresponding nuclear Hoescht fluorescence (L, N). Bright field images were processed with Adobe Photoshop CS2 in order to superimpose the N-tubulin expression (yellow) to the Hoescht fluorescence. Yellow arrows point to the projection emerging from the dorsal neural tube; cyan arrows point to both sides of the ventral neural tube; green arrows point to the place left by the disorganised or absent notochord; no, notochord; is, injected side; nis, non-injected side. (O, P) Summary of the results shown in A–J. doi:10.1371/journal.pone.0110559.g009
	Figure 10. Summary of the phenotypes after manipulating foxA4 function in Xenopus embryos. The diagrams show the phenotypes in embryos with normal (A, D), depleted (B, E), or excess levels (C, F) of foxA4 function, as revealed by the expression patterns of bra, chd, myf5/myoD, gsc, frzb1, otx2, Xanf1, krox20 and en2 at neural plate stage. (A–C) In DML development, foxA4 is necessary to restrict the paraxial mesodermal (PAM) and the prechordal mesodermal (PM) fates, allowing notochord (NO) development. (D–F) Controlled levels of foxA4 function are necessary for the correct specification and segregation of the anterior neural and ectodermal anlagen. ANR, anterior neural ridge; SHA, stomodeal-adenohypophyseal anlage; CGA, cement gland anlage; r3, third rhombomere; m/h, midbrain/hindbrain boundary. The asterisk in D marks the expression hole left by otx2 in the ANR, which is occupied by Xanf1. The dotted blue line (D–F) represents the contour of the neural plate. The dashed black line (D–F) represents the anterior boundary of the neural ectoderm. (A–C) Dorsal views. (D–F) Anterior views. See text for details. doi:10.1371/journal.pone.0110559.g010
	Figure 11. FoxA4 depletion induced robust cell death in the cephalic region.TUNEL analysis of stage 28 embryos injected with 20 ng of CtrlMO or FoxA4MO prior to the first cleavage. (A–D) Anterior views. (E–H) Lateral views of the same embryos shown in A–D, cleared in Murray's solution. CtrlMO-injected embryos showed scattered apoptotic cells (blue dots) (A, E). FoxA4MO-injected siblings presented accumulation of apoptotic cells in the head region (42%, n = 12) (B–D, F–H).
	Figure 12. FoxA4MO reproduced the effects on anterior neural markers in embryos in which mesoderm induction was blocked with Cer-S.(A–D) Expression of foxA4 in sibling controls (A, C) or in embryos injected with Cer-S mRNA (B, D), analysed at stage 9 (A, B) or at stage 11 (C, D). After blocking mesoderm induction, foxa4 expression persisted in the BCNE (B) (100%, n = 15) but was suppressed from the axial mesoderm (D) (100%, n = 7). (E, F) MyoD expression at neural plate stage in a sibling control (E) and in an embryo injected with Cer-S. Mesoderm was suppressed in 100% of the injected embryos analyzed with myoD (100%, n = 8). (G–I) Expression of Xanf1 and en2 at neural plate stage in a sibling control (G), and in embryos in which mesoderm induction was blocked with Cer-S and were injected at the 1-cell stage with either 20 ng of CtrlMO (H) or 20 ng of FoxA4MO (I). Embryos injected with CtrlMO + Cer-S showed expression of Xanf1 (yellow arrow) and en2 (black arrow) (H, 100%, n = 8). In embryos injected with FoxA4MO + Cer-S, Xanf1 was expanded and up-regulated (yellow arrow) and en2 was down-regulated (black arrow) (I, 100%, n = 10) in comparison to embryos injected with CtrlMO + Cer-S (H). (J–L) Expression of otx2 at neural plate stage in a sibling control (J), and in embryos in which mesoderm induction was blocked with Cer-S and were injected at the 1-cell stage with either 20 ng of Ctrl MO (K) or 20 ng of FoxA4MO (L). Embryos injected with CtrlMO + Cer-S showed expression of otx2 (K, 100%, n = 4). In embryos injected with FoxA4MO + Cer-S, otx2 was down-regulated (L, 100%, n = 20) in comparison to embryos injected with CtrlMO + Cer-S (K).
	Figure 13. Depletion of FoxA4 from the ectoderm expands Xanf1 and suppresses en2 in the anterior neural plate.(A) Embryos were injected at the 1-cell stage with 20 ng of FoxA4MO +20 ng of DOG (green) or were left uninjected (grey). At stage 9, ectodermal explants were excised and the following recombinants were obtained: in Control recombinants, the ectodermal explant of a recipient uninjected embryo was replaced with the ectodermal explant from an uninjected donor. In FoxA4MO ect/Control mes recombinant, the ectoderm was provided by a FoxA4MO-injected donor (green), while the mesoderm derived from an uninjected sibling recipient (grey). In Control ect/FoxA4MO mes recombinant, the ectoderm was provided by an uninjected sibling donor (grey), while the mesoderm derived from a FoxA4MO-injected recipient (green). (B–E′) Analysis of Xanf1 and en2 when uninjected sibling controls (B) reached neurula stage. (C,C′) Control recombinant. (D–D′) FoxA4MO ect/Control mes recombinant. (E–E′) Control ect/FoxA4MO mes recombinant. (D′ and E′) DOG fluorescence of the images shown in D′, E′, respectively.
	Figure 14. Model for foxA4 function in Xenopus embryos.(A) Summary of foxA4 functions in A–P regionalisation and in DML development. For simplicity, they are depicted in a diagram of an embryo at neural plate stage, shown in dorsal view, when foxA4 is only expressed in the DML (pink). FoxA4 modulates A–P development by inhibiting anterior fates (red lines) in the axial mesoderm (prechordal mesoderm, PM) and in the neuroectoderm (NE) and ectoderm, while favouring posterior fates (green arrows) in the neural plate and the dorsal midline (notochord, NO; floor plate, FP). In the trunk, foxA4 prevents the respecification of dorsal midline precursors towards contiguous fates, by inhibiting (red lines) the paraxial mesodermal fate (PAM). Yellow, prechordal mesoderm. Grey, paraxial mesoderm. The dotted light blue line demarcates de neural plate. (B) Diagram of a blastula stage embryo in dorsal view, showing the expression of foxA4 in the BCNE centre (pink), which is composed by precursors of the Spemann's organiser and of the whole forebrain and most of the midbrain and hindbrain [37]. An, animal; Veg, vegetal. FoxA4 modulates the initial CNS regionalisation by operating on the BCNE, favouring posterior fates among BCNE derivatives (green arrow), while restricting anterior fates (red line), as revealed by the markers Xanf1 (rostral forebrain), otx2 (caudal forebrain/midbrain), en2 (midbrain/hindbrain boundary).
	Figure 1. FoxA4 depletion altered the expression of mesodermal markers, impaired axis elongation, expanded the prechordal mesoderm and reduced the notochord.(A–J) Expression of mesodermal markers at stage 13, dorsal views. (A, F) myod. (B, G) bra. (C, H) gsc. (D, I) frzb1. (E, J) chd. Embryos were injected into one dorsal cell at the 4-cell stage with 40 ng of CtrlMO (A) or of FoxA4MO (B), or with 20 ng of each MO into both dorsal cells at the 4-cell stage, (CtrlMO: B,C,E; FoxA4MO: G, H, J) or at the 1-cell stage (CtrlMO: D; FoxA4MO: I). The myoD domain was shortened on the injected side (is) by FoxA4MO (58%, n = 12) (F). The bra domain was split by FoxA4MO (G) (79%, n = 24). The gsc domain was posteriorly expanded by FoxA4MO (100%, n = 15) (H). The frzb1 domain was posteriorly expanded by FoxA4MO (100%, n = 14) (I). The chd domain was affected in 100% of the injected embryos (n = 14) (J). Among these, 71% showed an expansion of the anterior chd domain, corresponding to the PM (green arrow), while the posterior domain (corresponding to the notochord) was severely reduced (red arrow). In the remaining 29%, the entire axial mesoderm appeared much thinner and shorter than in CtrlMO-injected siblings (inset in J). Similar results were obtained after injection of 20 ng of FoxA4MO into 1-cell stage embryos (Fig. S1B). (K) The body length between the cement gland and the tip of the tailbud was measured at tailbud stage in embryos injected before the first cleavage with 20 ng of CtrlMO (green bar, n = 25) or of FoxA4MO (red bar, n = 27). P<0.0001, two-tailed t-test. (L) Notochord/embryo length ratio measured in the group of embryos corresponding to those shown in (B, G). Green bar, CtrlMO (n = 18); red bar, FoxA4MO (n = 24). P<0.0001, two-tailed t-test. (M–R) Expression of axial mesodermal markers at stage 10.25. (M, P) gsc. (N, Q) frzb1. (O, R) chd. Embryos were injected with 20 ng of CtrlMO (M–O) or of FoxA4MO (P–R). Injections were performed unilaterally in 1 cell at the 2 or 4-cell stage or at the 1-cell stage, giving similar results. Unilateral injections are shown here. The injected side was identified by DOG fluorescence and is oriented to the right (insets in M–R). In gastrulae, we were able to observe an expansion of gsc (58%, n = 40; P) and of frzb1 domains (88%, n = 33; Q). chd expression was reduced in the less involuted, superficial cells on the injected side (red arrows), but a cloud of deep cells expressing chd persisted (green arrows), and even appeared to be expanded on the injected side in some embryos, like the one shown below (50%, n = 10) (R).

Acosta, Notch destabilises maternal beta-catenin and restricts dorsal-anterior development in Xenopus. 2011, Pubmed, Xenbase

Acosta, Notch destabilises maternal beta-catenin and restricts dorsal-anterior development in Xenopus. 2011, Pubmed , Xenbase
Ang, The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. 1993, Pubmed
Ang, HNF-3 beta is essential for node and notochord formation in mouse development. 1994, Pubmed
Artinger, Interaction of goosecoid and brachyury in Xenopus mesoderm patterning. 1997, Pubmed , Xenbase
Benayoun, Forkhead transcription factors: key players in health and disease. 2011, Pubmed
Blitz, Anterior neurectoderm is progressively induced during gastrulation: the role of the Xenopus homeobox gene orthodenticle. 1995, Pubmed , Xenbase
Britto, A critical role for sonic hedgehog signaling in the early expansion of the developing brain. 2002, Pubmed
Carron, Antagonistic interaction between IGF and Wnt/JNK signaling in convergent extension in Xenopus embryo. 2005, Pubmed , Xenbase
Charrier, Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis. 2001, Pubmed
Charrier, Dual origin of the floor plate in the avian embryo. 2002, Pubmed , Xenbase
Charrier, Cellular dynamics and molecular control of the development of organizer-derived cells in quail-chick chimeras. 2005, Pubmed
Cleaver, Notochord patterning of the endoderm. 2001, Pubmed , Xenbase
Dal-Pra, FoxA transcription factors are essential for the development of dorsal axial structures. 2011, Pubmed
Dale, Fate map for the 32-cell stage of Xenopus laevis. 1987, Pubmed , Xenbase
Dickinson, Positioning the extreme anterior in Xenopus: cement gland, primary mouth and anterior pituitary. 2007, Pubmed , Xenbase
Dirksen, A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain. 1992, Pubmed , Xenbase
Ekker, Distinct expression and shared activities of members of the hedgehog gene family of Xenopus laevis. 1995, Pubmed , Xenbase
Ermakova, The homeobox gene, Xanf-1, can control both neural differentiation and patterning in the presumptive anterior neurectoderm of the Xenopus laevis embryo. 1999, Pubmed , Xenbase
Ermakova, The homeodomain factor Xanf represses expression of genes in the presumptive rostral forebrain that specify more caudal brain regions. 2007, Pubmed , Xenbase
Franco, Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis. 1999, Pubmed , Xenbase
Godsave, Expression patterns of Hoxb genes in the Xenopus embryo suggest roles in anteroposterior specification of the hindbrain and in dorsoventral patterning of the mesoderm. 1994, Pubmed , Xenbase
Hallonet, Maintenance of the specification of the anterior definitive endoderm and forebrain depends on the axial mesendoderm: a study using HNF3beta/Foxa2 conditional mutants. 2002, Pubmed
Harland, In situ hybridization: an improved whole-mount method for Xenopus embryos. 1991, Pubmed , Xenbase
Hemmati-Brivanlou, Cephalic expression and molecular characterization of Xenopus En-2. 1991, Pubmed , Xenbase
Hensey, A developmental timer that regulates apoptosis at the onset of gastrulation. 1997, Pubmed , Xenbase
Hogan, Blood vessel patterning at the embryonic midline. 2004, Pubmed
Holland, Chordate origins of the vertebrate central nervous system. 1999, Pubmed
Hopwood, MyoD expression in the forming somites is an early response to mesoderm induction in Xenopus embryos. 1989, Pubmed , Xenbase
Hopwood, Xenopus Myf-5 marks early muscle cells and can activate muscle genes ectopically in early embryos. 1991, Pubmed , Xenbase
Ishibashi, Expression of Siamois and Twin in the blastula Chordin/Noggin signaling center is required for brain formation in Xenopus laevis embryos. 2008, Pubmed , Xenbase
Kablar, Xotx genes in the developing brain of Xenopus laevis. 1996, Pubmed , Xenbase
Kaestner, Unified nomenclature for the winged helix/forkhead transcription factors. 2000, Pubmed
Kazanskaya, Anf: a novel class of vertebrate homeobox genes expressed at the anterior end of the main embryonic axis. 1997, Pubmed , Xenbase
Keller, How we are shaped: the biomechanics of gastrulation. 2003, Pubmed , Xenbase
Keller, The forces that shape embryos: physical aspects of convergent extension by cell intercalation. 2008, Pubmed , Xenbase
Kimura-Yoshida, Crucial roles of Foxa2 in mouse anterior-posterior axis polarization via regulation of anterior visceral endoderm-specific genes. 2007, Pubmed
Kishi, Requirement of Sox2-mediated signaling for differentiation of early Xenopus neuroectoderm. 2000, Pubmed , Xenbase
Knöchel, Activin A induced expression of a fork head related gene in posterior chordamesoderm (notochord) of Xenopus laevis embryos. 1992, Pubmed , Xenbase
Kuroda, Neural induction in Xenopus: requirement for ectodermal and endomesodermal signals via Chordin, Noggin, beta-Catenin, and Cerberus. 2004, Pubmed , Xenbase
Kwan, Xbra functions as a switch between cell migration and convergent extension in the Xenopus gastrula. 2003, Pubmed , Xenbase
Latimer, Notch signaling regulates midline cell specification and proliferation in zebrafish. 2006, Pubmed
Latinkic, Goosecoid and mix.1 repress Brachyury expression and are required for head formation in Xenopus. 1999, Pubmed , Xenbase
Leyns, Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer. 1997, Pubmed , Xenbase
Luu, Control of gastrula cell motility by the Goosecoid/Mix.1/ Siamois network: basic patterns and paradoxical effects. 2008, Pubmed , Xenbase
López, Retinoic acid induces changes in the localization of homeobox proteins in the antero-posterior axis of Xenopus laevis embryos. 1992, Pubmed , Xenbase
López, The Notch-target gene hairy2a impedes the involution of notochordal cells by promoting floor plate fates in Xenopus embryos. 2005, Pubmed , Xenbase
Martynova, Patterning the forebrain: FoxA4a/Pintallavis and Xvent2 determine the posterior limit of Xanf1 expression in the neural plate. 2004, Pubmed , Xenbase
Mizuseki, Xenopus Zic-related-1 and Sox-2, two factors induced by chordin, have distinct activities in the initiation of neural induction. 1998, Pubmed , Xenbase
Monuki, The morphogen signaling network in forebrain development and holoprosencephaly. 2007, Pubmed
Morgan, Transposon tools for recombinant DNA manipulation: characterization of transcriptional regulators from yeast, Xenopus, and mouse. 1996, Pubmed , Xenbase
Muenke, Genetics of ventral forebrain development and holoprosencephaly. 2000, Pubmed
Murato, Two alloalleles of Xenopus laevis hairy2 gene--evolution of duplicated gene function from a developmental perspective. 2007, Pubmed , Xenbase
Nagatomo, Xenopus hairy2 functions in neural crest formation by maintaining cells in a mitotic and undifferentiated state. 2007, Pubmed , Xenbase
Nieto, Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction. 1991, Pubmed , Xenbase
Norton, Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones. 2005, Pubmed
Odenthal, fork head domain genes in zebrafish. 1998, Pubmed
Pannese, The Xenopus homologue of Otx2 is a maternal homeobox gene that demarcates and specifies anterior body regions. 1995, Pubmed , Xenbase
Pannese, The Xenopus Emx genes identify presumptive dorsal telencephalon and are induced by head organizer signals. 1998, Pubmed , Xenbase
Papalopulu, A posteriorising factor, retinoic acid, reveals that anteroposterior patterning controls the timing of neuronal differentiation in Xenopus neuroectoderm. 1996, Pubmed , Xenbase
Patten, Distinct modes of floor plate induction in the chick embryo. 2003, Pubmed
Pera, A direct screen for secreted proteins in Xenopus embryos identifies distinct activities for the Wnt antagonists Crescent and Frzb-1. 2000, Pubmed , Xenbase
Peres, Interaction between X-Delta-2 and Hox genes regulates segmentation and patterning of the anteroposterior axis. 2006, Pubmed , Xenbase
Piccolo, The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. 1999, Pubmed , Xenbase
Pizard, Whole-mount in situ hybridization and detection of RNAs in vertebrate embryos and isolated organs. 2004, Pubmed , Xenbase
Pohl, Of Fox and Frogs: Fox (fork head/winged helix) transcription factors in Xenopus development. 2005, Pubmed , Xenbase
Reversade, Depletion of Bmp2, Bmp4, Bmp7 and Spemann organizer signals induces massive brain formation in Xenopus embryos. 2005, Pubmed , Xenbase
Revinski, Delta-Notch signaling is involved in the segregation of the three germ layers in Xenopus laevis. 2010, Pubmed , Xenbase
Ruiz i Altaba, Pintallavis, a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis. 1992, Pubmed , Xenbase
Ruiz i Altaba, Ectopic neural expression of a floor plate marker in frog embryos injected with the midline transcription factor Pintallavis. 1993, Pubmed , Xenbase
Ruiz i Altaba, Sequential expression of HNF-3 beta and HNF-3 alpha by embryonic organizing centers: the dorsal lip/node, notochord and floor plate. 1993, Pubmed , Xenbase
Ruiz i Altaba, Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. 1998, Pubmed , Xenbase
Saka, A screen for targets of the Xenopus T-box gene Xbra. 2000, Pubmed , Xenbase
Sasai, Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. 1994, Pubmed , Xenbase
Sasaki, Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. 1993, Pubmed
Schäfer, Medial floor plate formation in zebrafish consists of two phases and requires trunk-derived Midkine-a. 2005, Pubmed
Sive, Progressive determination during formation of the anteroposterior axis in Xenopus laevis. 1989, Pubmed , Xenbase
Strähle, Vertebrate floor-plate specification: variations on common themes. 2004, Pubmed
Tada, Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. 2000, Pubmed , Xenbase
Teillet, The relationships between notochord and floor plate in vertebrate development revisited. 1998, Pubmed
Theveneau, Collective cell migration of the cephalic neural crest: the art of integrating information. 2011, Pubmed
Thibert, Inhibition of neuroepithelial patched-induced apoptosis by sonic hedgehog. 2003, Pubmed
Wallingford, Xenopus Dishevelled signaling regulates both neural and mesodermal convergent extension: parallel forces elongating the body axis. 2001, Pubmed , Xenbase
Wardle, Cement gland-specific activation of the Xag1 promoter is regulated by co-operation of putative Ets and ATF/CREB transcription factors. 2002, Pubmed , Xenbase
Weigel, The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. 1989, Pubmed
Weigel, The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? 1990, Pubmed
Weinstein, The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo. 1994, Pubmed
Wessely, Neural induction in the absence of mesoderm: beta-catenin-dependent expression of secreted BMP antagonists at the blastula stage in Xenopus. 2001, Pubmed , Xenbase
Wessely, Analysis of Spemann organizer formation in Xenopus embryos by cDNA macroarrays. 2004, Pubmed , Xenbase
Wijchers, In control of biology: of mice, men and Foxes. 2006, Pubmed
Wilson, Early steps in the development of the forebrain. 2004, Pubmed
Yamaguti, Xenopus hairy2b specifies anterior prechordal mesoderm identity within Spemann's organizer. 2005, Pubmed , Xenbase
Yang, Roles of organizer factors and BMP antagonism in mammalian forebrain establishment. 2006, Pubmed
Yusuf, The eventful somite: patterning, fate determination and cell division in the somite. 2006, Pubmed
Zaraisky, The homeobox-containing gene XANF-1 may control development of the Spemann organizer. 1995, Pubmed , Xenbase
Zhou, Cloning and expression of xSix3, the Xenopus homologue of murine Six3. 2000, Pubmed , Xenbase
de-Leon, The conserved role and divergent regulation of foxa, a pan-eumetazoan developmental regulatory gene. 2011, Pubmed