<i>Hand2</i>is necessary for terminal differentiation of enteric neurons from crest-derived precursors but not for their migration into the gut or for formation of glia

D’Autréaux, Fabien; Morikawa, Yuka; Cserjesi, Peter; Gershon, Michael D.

doi:10.1242/dev.003814

Cited by 69 publications

(73 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed a similar, but more complete, coincidence of Sox10 and Phox2b in the pancreas, possibly reflecting a more synchronous arrival and differentiation of neural crest cells in the pancreas. As in the gut (D'Autreaux et al, 2007), markers of differentiated neurons and glia then appeared shortly thereafter, along with lineage-specific markers, such as the bHLH transcription factor Hand2 (data not shown).…”

Section: Discussionmentioning

confidence: 89%

Signals from the neural crest regulate beta-cell mass in the pancreas

et al. 2008

View full text Add to dashboard Cite

*Pancreatic islet cells and neurons share common functions and similar ontogenies, but originate in different germ layers. To determine whether ectoderm-derived cells contribute instructive signals to the developing endoderm-derived pancreas, we defined the chronology of migration and differentiation of neural crest cells in the pancreas, and tested their role in the development of the islets. The homeodomain transcription factor Phox2b marks the neural precursors from the neural crest that colonize the gut to form the enteric nervous system. In the embryonic mouse pancreas, we found Phox2b expressed briefly together with Sox10 along the epithelial-mesenchymal border at E12.5 in cells derived from the neural crest. Downregulation of Phox2b shortly thereafter was dependent upon Nkx2.2 expressed in the adjacent pancreatic epithelium. In Phox2b -/-embryos, neurons and glia did not develop in the pancreas, and Nkx2.2 expression was markedly upregulated in the epithelium. In addition, the number and replication rate of insulin-expressing beta-cells increased in the Phox2b -/-mice. We conclude that, during pancreatic development, Phox2b and Nkx2.2 form a non-cell-autonomous feedback loop that links the neural crest with the pancreatic epithelium, regulates the size of the beta-cell population, and thereby impacts insulin-secretory capacity and energy homeostasis.

show abstract

Section: Discussionmentioning

confidence: 89%

Signals from the neural crest regulate beta-cell mass in the pancreas

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Conditional ablation of Hand2 in NCCs has revealed a crucial role for Hand2 in the development of sympathetic ganglion neurons (Hendershot et al, 2008;Morikawa et al, 2007), the enteric nervous system (Hendershot et al, 2007;D'Autreaux et al, 2007) and the cardiac outflow tract (Holler et al, 2010). In addition, conditional inactivation of Hand2 in the developing palatal epithelium has uncovered a role for Hand2 in palatal shelf fusion (Xiong et al, 2009).…”

Section: Ba/bamentioning

confidence: 99%

Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis

et al. 2011

View full text Add to dashboard Cite

SUMMARYLower jaw development is a complex process in which multiple signaling cascades establish a proximal-distal organization. These cascades are regulated both spatially and temporally and are constantly refined through both induction of normal signals and inhibition of inappropriate signals. The connective tissue of the tongue arises from cranial neural crest cell-derived ectomesenchyme within the mandibular portion of the first pharyngeal arch and is likely to be impacted by this signaling. Although the developmental mechanisms behind later aspects of tongue development, including innervation and taste acquisition, have been elucidated, the early patterning signals driving ectomesenchyme into a tongue lineage are largely unknown. We show here that the basic helix-loop-helix transcription factor Hand2 plays key roles in establishing the proximaldistal patterning of the mouse lower jaw, in part through establishing a negative-feedback loop in which Hand2 represses Dlx5 and Dlx6 expression in the distal arch ectomesenchyme following Dlx5-and Dlx6-mediated induction of Hand2 expression in the same region. Failure to repress distal Dlx5 and Dlx6 expression results in upregulation of Runx2 expression in the mandibular arch and the subsequent formation of aberrant bone in the lower jaw along with proximal-distal duplications. In addition, there is an absence of lateral lingual swelling expansion, from which the tongue arises, resulting in aglossia. Hand2 thus appears to establish a distal mandibular arch domain that is conducive for lower jaw development, including the initiation of tongue mesenchyme morphogenesis.

show abstract

“…Previous studies have identified molecules that can affect the differentiation of enteric neural crest-derived cells into enteric neurons (Blaugrund et al, 1996;Chalazonitis et al, 2004Chalazonitis et al, , 2008D'Autreaux et al, 2007;Okamura and Saga, 2008). For example, the disruption of the Notch signalling pathway has recently been shown to result in premature neurogenesis and a decrease in gliogenesis (Okamura and Saga, 2008).…”

Section: Cgrpmentioning

confidence: 99%

“…A similar result was obtained in mice that lack the transcription factor, Hand2 (D' Autreaux et al, 2007). In Hand2 knockout mice, enteric neurons fail to develop, however the de- velopmental appearance and density of enteric glial cells was not affected (D'Autreaux et al, 2007). Endothelin-3 inhibits the neuronal differentiation of enteric neural crestderived cells in vitro Wu et al, 1999), and mice lacking endothin-3 have delayed migration of crest-derived cells along the developing gut (Kapur et al, 1992(Kapur et al, , 1993Barlow et al, 2003).…”

Section: Cgrpmentioning

confidence: 99%

“…The expression of particular transcription factors have been shown to determine the prospective phenotype of the neural crest-derived cells. For example, the transcription factor, Hand2, is required for neural crest-derived cells to differentiate into enteric neurons but not glial cells (D'Autreaux et al, 2007). Mash1 is required for the development of enteric serotonergic neurons, but not for calcitonin gene-related peptide (CGRP) neurons (Blaugrund et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cell adhesion molecule L1 affects the rate of differentiation of enteric neurons in the developing gut

Turner

Schachner

Anderson

2009

Developmental Dynamics

View full text Add to dashboard Cite

The enteric nervous system arises predominantly from vagal level neural crest cells that migrate into and along the developing gut. As the neural crest-derived cells migrate within the gut, a subpopulation begins to differentiate into enteric neurons. Here, we show that the differentiation of neural crest-derived cells into enteric neurons is delayed in L1-deficient mice, compared with littermate controls. However, glial cell differentiation is not affected in L1-deficient mice. These mice also show a delay in the differentiation of a neurotransmitter-specific subtype of enteric neuron within the gastrointestinal tract. Together, these results suggest a role for the cell adhesion molecule, L1, in the differentiation of neural crestderived cells into enteric neurons within the developing enteric nervous system. Developmental Dynamics 238:708 -715, 2009.

show abstract

Hand2is necessary for terminal differentiation of enteric neurons from crest-derived precursors but not for their migration into the gut or for formation of glia

Cited by 69 publications

References 66 publications

Signals from the neural crest regulate beta-cell mass in the pancreas

Signals from the neural crest regulate beta-cell mass in the pancreas

Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis

Cell adhesion molecule L1 affects the rate of differentiation of enteric neurons in the developing gut

Contact Info

Product

Resources

About