Functional analysis of Hairy genes in Xenopus neural crest initial specification and cell migration

Abstract

Background: Neural crest formation is one of the fundamental processes in the early stages of embryonic development in vertebrates. This transient and multipotent embryonic cell population is able to generate a variety of tissues and cell types in the adult body. hairy genes are transcription factors that contain a basic helix-loop-helix domain which binds to DNA. In Xenopus three hairy genes are known: hairy1, hairy2a, and hairy2b. The requirement of hairy genes was explored in early neural crest development although the late requirements of these genes during neural crest maintenance, migration and derivatives formation are still unknown. Results: In this work, we extended the analysis of Xenopus hairy genes expression patterns and described new domains of expression. Functional analysis showed that hairy genes are required for the induction and migration of the neural crest and for the control of apoptosis. Moreover, we showed that hairy genes function as transcriptional repressors and that they are down-regulated by bone morphogenetic protein-Smad signaling and positively regulated by the Notch/Delta-Su(h) pathway. Conclusions: Our results indicate that hairy genes have a functional equivalence between them and that they are required for multiple processes during neural crest development. Developmental Dynamics 244:988-1013, 2015. V C 2015 Wiley Periodicals, Inc.

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

“…In other organs/tissues, several reports have shown that Hes4 is expressed in the stem/progenitor cells and is involved in their differentiation, migration, maintenance of undifferentiated state, and so on. . Our study here revealed that some cells expressing Hairy2b were located just beneath the adult stem/progenitor cells in the metamorphosing intestine.…”

“…Inhibition of Notch signaling by DBZ dramatically suppressed TH‐induced up‐regulation of Hairy genes, confirming their Notch dependency . Internal hemorrhage around the nose and along the digits of hindlimb in the DBZ‐treated tadpoles may also be suggestive of Notch inhibition in those organs/tissues since it has been shown that loss of Notch1 causes vascular tumors and lethal hemorrhage in mouse .…”

Comparative Functional Analysis of the Basic Helix-Loop-Helix Proteins in the Clawed Frogs' Genomes With Common Essential Pathways and Enriched Gene Ontology Terms

“…Previous studies have revealed that the maternally supplied Ascl1 was capable to set a pre-patterning tendency for frog embryonic cells to adopt neural fates and represses the mesendoderm formation via the HDAC-dependent antagonism of frog VegT (Gao et al, 2016;Min et al, 2016). On the other hand, the hairy genes are key bHLH transcription factors required in the early neural crest development of clawed frogs (Vega-López et al, 2015), whereas neural crest formation is one of the fundamental processes in the early stages of the frog embryonic development to generate a variety of tissues and cell types.…”

The role of teratogens in neural crest development

“…The effect of low FA, a methyl donor, on the neural plate and NC is through epigenetic demethylation and further activation of the Hes1 gene (a Notch pathway target). Research in Xenopus and mouse ESC have shown that homologues of the Hes1 protein are involved in the development of the NC, controlling essential genes required for the differentiation of this cell population (Mendez‐Maldonado, Vega‐Lopez, Caballero‐Chacon, Aybar, & Velasco, ; Vega‐López et al, ). Another mechanism is the increase of cell proliferation and integrin adhesion, and decrease in BMP4 signaling and apoptosis through p53 inhibition (Aujla, Bora, Monahan, Sweedler, & Raetzman, ; Klinck et al, ; Zhu et al, ).…”