Differential requirement of bone morphogenetic protein receptors Ia (ALK3) and Ib (ALK6) in early embryonic patterning and neural crest development

Background Bone morphogenetic proteins regulate multiple processes in embryonic development, including early dorso-ventral patterning and neural crest development. BMPs activate heteromeric receptor complexes consisting of type I and type II receptor-serine/threonine kinases. BMP receptors Ia and Ib, also known as ALK3 and ALK6 respectively, are the most common type I receptors that likely mediate most BMP signaling events. Since early expression patterns and functions in Xenopus laevis development have not been described, we have addressed these questions in the present study. Results Here we have analyzed the temporal and spatial expression patterns of ALK3 and ALK6; we have also carried out loss-of-function studies to define the function of these receptors in early Xenopus development. We detected both redundant and non-redundant roles of ALK3 and ALK6 in dorso-ventral patterning. From late gastrula stages onwards, their expression patterns diverged, which correlated with a specific, non-redundant requirement of ALK6 in post-gastrula neural crest cells. ALK6 was essential for induction of neural crest cell fate and further development of the neural crest and its derivatives. Conclusions ALK3 and ALK6 both contribute to the gene regulatory network that regulates dorso-ventral patterning; they play partially overlapping and partially non-redundant roles in this process. ALK3 and ALK6 are independently required for the spatially restricted activation of BMP signaling and msx2 upregulation at the neural plate border, whereas in post-gastrula development ALK6 exerts a highly specific, conserved function in neural crest development

PAPC and the Wnt5a/Ror2 pathway control the invagination of the otic placode in Xenopus

<p>Abstract</p> <p>Background</p> <p>Paraxial protocadherin (PAPC) plays a crucial role in morphogenetic movements during gastrulation and somitogenesis in mouse, zebrafish and Xenopus. PAPC influences cell-cell adhesion mediated by C-Cadherin. A putative direct adhesion activity of PAPC is discussed. PAPC also promotes cell elongation, tissue separation and coordinates cell mass movements. In these processes the signaling function of PAPC in activating RhoA/JNK and supporting Wnt-11/PCP by binding to frizzled 7 (fz7) is important.</p> <p>Results</p> <p>Here we demonstrate by loss of function experiments in Xenopus embryos that PAPC regulates another type of morphogenetic movement, the invagination of the ear placode. Knockdown of PAPC by antisense morpholinos results in deformation of the otic vesicle without altering otocyst marker expression. Depletion of PAPC could be rescued by full-length PAPC, constitutive active RhoA and by the closely related PCNS but not by classical cadherins. Also the cytoplasmic deletion mutant M-PAPC, which influences cell adhesion, does not rescue the PAPC knockdown. Interestingly, depletion of Wnt5a or Ror2 which are also expressed in the otocyst phenocopies the PAPC morphant phenotype.</p> <p>Conclusions</p> <p>PAPC signaling via RhoA and Wnt5a/Ror2 activity are required to keep cells aligned in apical-basal orientation during invagination of the ear placode. Since neither the cytoplasmic deletion mutant M-PAPC nor a classical cadherin is able to rescue loss of PAPC we suggest that the signaling function of the protocadherin rather than its role as modulator of cell-cell adhesion is required during invagination of the ear placode.</p

Cystein-reiche sekretorische Proteine (CRISPs) des männlichen Genitaltrakts von Pferd und Schwein

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Dishevelled Paralogs in Vertebrate Development: Redundant or Distinct?

Dishevelled (DVL) proteins are highly conserved in the animal kingdom and are important key players in β-Catenin-dependent and -independent Wnt signaling pathways. Vertebrate genomes typically comprise three DVL genes, DVL1, DVL2, and DVL3. Expression patterns and developmental functions of the three vertebrate DVL proteins however, are only partially redundant in any given species. Moreover, expression and function of DVL isoforms have diverged between different vertebrate species. All DVL proteins share basic functionality in Wnt signal transduction. Additional, paralog-specific interactions and functions combined with context-dependent availability of DVL isoforms may play a central role in defining Wnt signaling specificity and add selectivity toward distinct downstream pathways. In this review, we recapitulate briefly cellular functions of DVL paralogs, their role in vertebrate embryonic development and congenital disease

Characterizing the robo signalling cascade that drives direct neurogenesis

Resumen del póster presentado al European Developmental Biology Congress (EDBC), celebrado en Alicante del 23 al 26 de octubre de 2019.The Genetic and molecular mechanisms that control development and increased size of the cerebral cortex along amniote evolution are largely unknown. Cortex size depends on neurons produced during embryonic development. Neurons are produced directly from Radial Glia Cells (RGCs), or indirectly from RGCs via generating Intermediate Progenitor Cells (IPCs). The balance between aRGC selfrenewal, production of IPCs or consumption toward neurogenesis, is under a complex set of regulatory mechanisms. Our previous studies in the mouse neocortex showed that very low levels of membrane receptors Robo1 and Robo2 are essential in controlling the balance between RGC self-renewal and production of IPCs. This is controlled partly by Robo driving Hes1 transcription, a component of Notch pathway. Recently, our lab showed high levels of Robo signalling in RGCs, concomitant with low Dll1 levels (ligand of Notch), promote direct neurogenesis with aRGC self-consumption, whereas inversion of these levels lead to indirect neurogenesis via production of IPCs. We further showed attenuation of Robo signalling was responsible for increasing neuron production and cortical expansion in vertebrate evolution. Here we investigate the intracellular interactome of Robo to characterize the molecular signalling pathway downstream of Robo activation that leads to direct neurogenesis. To this aim we are performing structurefunction analyses of the intracellular domain of Robo to identify the functional domains, and predicted interacting proteins, that are key in promoting direct neurogenesis upon Robo activation. Our findings should illuminate the mode of interaction between Robo and Notch signalling, two extensively studied signalling pathways not previously related.Peer reviewe

Additional file 6: Figure S6. of Differential requirement of bone morphogenetic protein receptors Ia (ALK3) and Ib (ALK6) in early embryonic patterning and neural crest development

Knock-down of ALK3 in the dorsal ectoderm results in an expansion of neural tissue. (PDF 159 kb