To be able to overcome this lethality, mutant mice were engineered expressing ErbB4 only in the heart

To be able to overcome this lethality, mutant mice were engineered expressing ErbB4 only in the heart. to an important role of transcriptional regulators when neural differentiation occurs. However, some of these proteins have an important participation in malformations of the cranial portion and their mutation results in aberrant neurogenesis. This review aims to give an overview of the role of cell signaling and of the function of transcription factors LEQ506 involved in the specification of ganglia precursors and neurogenesis to form the NC-derived cranial nerves during organogenesis. genes is usually color-coded. On the right, signaling pathways and the expression of transcription factors involved in cranial nerve (CN) formation are indicated. Adapted from Lumsden and Keynes (1989), Noden (1991), Yamamoto and Schwarting (1991), Bally-Cuif and Wassef (1995), Takahashi and Osumi (2002), and Mller and ORahilly (2011). Abbreviations: CN, cranial nerve; FP, floor plate; M, mesencephalon; NCCs, neural crest cells; OV, otic vesicle; r, rhombomere; PA, pharyngeal arches. NC formation is a complex and multistep process initially directed by cell signaling molecules including Bone Morphogenetic Proteins (BMPs), Wnts (Wingless and Int-1), Fibroblast Growth Factor (FGF), and retinoic acid (RA). These signals reveal the tissue interactions into the ectodermal cell populations, the neural plate, the non-neural ectoderm, Rabbit Polyclonal to NMS and the underlying mesoderm in a highly coordinated manner (Vega-Lopez et al., 2017). It has been proposed that NC specification LEQ506 occurs during gastrulation as a consequence of the action of two successive gradients of secreted signals. A combination of intermediate levels of activity of BMP and Wnt signaling acting on the ectoderm to induce and specify NC precursors at the neural plate border, and a subsequent requirement of both signals is needed for maintenance of specification during neurulation (Aybar and Mayor, 2002; Steventon et al., 2009). In chick embryos, it was shown that NCCs are specified as early as the blastula stage (Prasad et al., 2020). It was exhibited that, during gastrulation, expression is restricted to cells located in a region in the medial epiblast, which are NC-fated and contribute to the neural folds and later to migrating NCCs (Basch et al., 2006). The inhibition of Pax7 function in chicks inhibited the expression of key NC markers such as (OMIM 602150), (Sry-box 9, OMIM 608160), (OMIM 602229), and (beta-1,3-glucuronyltransferase 1 like, OMIM 151290) (Basch and Bronner-Fraser, 2006). This LEQ506 evidence suggests that the neural plate-prospective ectoderm conversation at the neural plate border might not be a requisite for NC specification or induction, and that neural plate border formation and NC induction might be separable events. The various research works carried out to study the origin of NCCs have identified genes organized into a gene regulatory network that participate in and control the induction, specification and differentiation of NC (Sim?es-Costa et al., 2015). An example of this are the transcription factors involved in induction such as FoxD3 (((OMIM 609391), (OMIM 300265) and (OMIM 605802) had their induction and peak of expression before the classical neural plate border specifier genes such (OMIM 606597/167410) and (OMIM 600470). Such specifier genes, together with signaling molecules, direct the expression of NC-specific genes like (OMIM 107580), ((Microphthalmia-associated transcription factor, OMIM 156845)] in human NC development (Betters et al., 2010). The NC population migrates to different regions of the mouse embryo from the NT after the epithelial-mesenchymal transition, maintaining its multipotential character until completing differentiation in its final destination (Baggiolini et al., 2015). To study the ontogeny of the NC, different model organisms, both and have shown that there is an activity gradient of BMPs controlled by their antagonists and that an intermediate level is needed to induce the formation of the NC (LaBonne and Bronner-Fraser, 1998; Marchant et al., 1998; Barth et LEQ506 al., 1999; Tribulo et al., 2003). Thus, the BMP antagonists Chordin (OMIM 603475) and Noggin (OMIM 602991) are expressed in a spatio-temporal manner that influences the formation of the NC. In mouse, at embryonic day (E) 8.0, Noggin is expressed in the neural folds and in the dorsal region after the closure of the NT. The expression of Chordin is usually low at the level of the neural plate and in the paraxial mesoderm. These antagonists participate in the induction of NC as well as in delamination, but also protect from apoptosis induced by BMP during migration and differentiation of NCCs. Importantly, it was observed that this decrease in the expression of these BMP antagonists alters the PNS derived from the NC and craniofacial skeletal elements. Noggin knockout mice presented all cranial nerves, but the vagus (X) and glossopharyngeal (IX) are disorganized and fused. Double-knockout mice of Noggin and Chordin lack.