Dunwoodie SL et al. (1997), Mouse Dll3: a novel divergent Delta gene which ...

XB-ART-16168

Development 1997 Aug 01;12416:3065-76. doi: 10.1242/dev.124.16.3065.

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Mouse Dll3: a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo.

Dunwoodie SL , Henrique D , Harrison SM , Beddington RS .

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Mouse delta-like 3 (Dll3), a novel vertebrate homologue of the Drosophila gene Delta was isolated by a subtracted library screen. In Drosphila, the Delta/Notch signalling pathway functions in many situations in both embryonic and adult life where cell fate specification occurs. In addition, a patterning role has been described in the establishment of the dorsoventral compartment boundary in the wing imaginal disc. Dll3 is the most divergent Delta homologue identified to date. We confirm that Dll3 can inhibit primary neurogenesis when ectopically expressed in Xenopus, suggesting that it can activate the Notch receptor and therefore is a functional Delta homologue. An extensive expression study during gastrulation and early organogenesis in the mouse reveals a diverse and dynamic pattern of expression. The three major sites of expression implicate Dll3 in somitogenesis and neurogenesis and in the production of tissue from the primitive streak and tailbud. A careful comparison of Dll3 and Dll1 expression by double RNA in situ hybridisation demonstrates that these genes have distinct patterns of expression, but implies that together they operate in many of the same processes. We postulate that during somitogenesis Dll3 and Dll1 coordinate in establishing the intersomitic boundaries. We confirm that, during neurogenesis in the spinal cord, Dll1 and Dll3 are expressed by postmitotic cells and suggest that expression is sequential such that cells express Dll1 first followed by Dll3. We hypothesise that Dll1 is involved in the release of cells from the precursor population and that Dll3 is required later to divert neurons along a specific differentiation pathway.

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Species referenced: Xenopus
Genes referenced: dlc dll1 dlx5 egf gal.1 notch1 notch4 notch4.2 tubb2b

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Fig. 3. Alignment of predicted protein sequence of Dll3 and other Delta-like proteins. (A) Protein alignment between Dll3, Dll1 and Drosophila Delta. The DSL, EGF-like repeats and transmembrane domain (TM) are underlined. The EGF-like repeats are numbered according to Drosophila Delta. The conserved amino acids are shaded. (B) Alignment of the DSL region from all Delta like proteins. The conserved amino acids are shaded. Dll3, mouse Delta-like 3; Dll1, mouse Delta-like 1 (Bettenhausen et al., 1996); XD2. Xenopus Delta-2 (Jen et al., 1997); DD, Drosophila Delta (Kopczynski et al., 1988); APX1 (Mello et al., 1994) and LAG2 (Tax et al., 1994; Henderson et al., 1994) represent Delta like genes in C. elegans.

Fig. 4. Injection of Dll3 RNA inhibits primary neuron formation in Xenopus. (A-D) Neural plate stage Xenopus embryos (dorsal view, posterior to the right) showing N-tubulin gene expression (purple) identifying primary neurons, in medial (m), intermediate (i) and lateral (l) locations. A single injection of 50 pg of lacZ RNA and 200 pg of X-Delta-1 or Dll3 RNA into a 2- or 4-cell embryo gave localisation of the transcripts to different regions of the neural plate as shown by X-gal staining (bracket). (A) Ectopic expression of XDelta- 1 RNA supresses primary neuron formation. The lateral stripe of neurons (l) is absent in the region where X-Delta-1 RNA is localised, indicated by Xgal-positive cells (bracket). (B-D) Ectopic expression of Dll3 RNA supresses primary neuron formation. Lateral and intermediate neurons are reduced in number (B) or absent (C) where Dll3 RNA is localised (bracket). (D) Medial, intermediate and anterior lateral neurons are absent where Dll3 RNA is localised (bracket). Scale bar, 330 mm.