XB-ART-41017Dev Biol December 15, 2009; 336 (2): 280-92.
PRDC regulates placode neurogenesis in chick by modulating BMP signalling.
The epibranchial placodes generate the neurons of the geniculate, petrosal, and nodose cranial sensory ganglia. Previously, it has been shown that bone morphogenetic proteins (BMPs) are involved in the formation of these structures. However, it has been unclear as to whether BMP signalling has an ongoing function in directing the later development of the epibranchial placodes, and how this signalling is regulated. Here, we demonstrate that BMPs maintain placodal neurogenesis and that their activity is modulated by a member of the Cerberus/Dan family of BMP antagonists, Protein Related to Dan and Cerberus (PRDC). We find that Bmp4 is expressed in the epibranchial placodes while Bmp7 and PRDC are expressed in the pharyngeal pouches. The timing and regional expression of these three genes suggest that BMP7 is involved in inducing placode neurogenesis and BMP4 in maintaining it and that BMP activity is modulated by PRDC. To investigate this hypothesis, we have performed both gain- and loss- of-function experiments with PRDC and find that it can modulate the BMP signals that induce epibranchial neurogenesis: a gain of PRDC function results in a loss of Bmp4 and hence placode neurogenesis is inhibited; conversely, a loss of PRDC function induces ectopic Bmp4 and an expansion of placode neurogenesis. This modulation is therefore necessary for the number and positioning of the epibranchial neurons.
PubMed ID: 19836367
Article link: Dev Biol
Genes referenced: bmp4 bmp7.1 bmp7.2 cer1 egr2 emx1 emx1l hoxb9 hoxc9-like krt12.4 nbl1 nodal nodal1 otx2 sia1 tbxt wnt8a
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|Fig. 2. Overexpression of cPRDC in X. laevis. (A) Embryos were injected at the 4-cell stage in the ventral marginal zone with 1 ng chick PRDC RNA and left to develop until early tadpole stages. All control embryos are in the left hand panel, and PRDC-injected in the right, asterisk indicates secondary axis. (i) Uninjected control embryo compared to PRDC-injected embryo which has a partial secondary axis (marked with an ). Embryos were analysed for a variety of anterior–posterior markers: Hoxb9 (ii), Krox20 (iii), Otx2 (iv), and Emx1 (v). Arrows in (ii) and (iii) show the Hoxb9 and Krox20 gene expression in the secondary axis. White arrows in (v) indicate the lack of Emx1 forebrain expression, whereas the black arrow shows the kidney expression of Emx1. (B) PRDC can inhibit Bmp4 and Bmp7 but not Wnt8, as demonstrated by the coinjection of PRDC with these genes and the analysis of their immediate downstream targets. PRDC blocked the induction of brachyury (Xbra) and epidermal keratin (EK) by Bmp4 and 7, but not the induction of Siamois (Sia) and Xenopus nodal related-3 (Xnr3) by Wnt8 (see arrows). cg, cement gland; ey, eye; fb, forebrain; hb, hindbrain; ki, kidney; mb, midbrain; nc, neural crest; r3, rhombomere 3; r5, rhombomere 5; sc, spinal cord.|