NKX2 gene expression in neuroectoderm but not in mesendodermally derived structures depends on sonic hedgehog in mouse embryos

Pabst, Oliver; Herbrand, Heike; Takuma, Naoyuki; Arnold, Hans-Henning

doi:10.1007/pl00008188

Cited by 90 publications

(58 citation statements)

References 15 publications

(14 reference statements)

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“…8K,L, insets). This result, along with the defective induction of other SHH downstream genes such as Nkx2.1 (Pabst et al, 2000) (see Fig. 5), strengthens the idea that SHH signaling activity is deficient in the diencephalon of RA-deficient embryos.…”

Section: Ra Deficiency Affects Sonic Hedgehog Signaling In the Forebrainsupporting

confidence: 75%

Retinaldehyde dehydrogenase 2 (RALDH2)-mediated retinoic acid synthesis regulates early mouse embryonic forebrain development by controlling FGF and sonic hedgehog signaling

et al. 2006

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Although retinoic acid (RA) has been implicated as one of the diffusible signals regulating forebrain development, patterning of the forebrain has not been analyzed in detail in knockout mouse mutants deficient in embryonic RA synthesis. We show that the retinaldehyde dehydrogenase 2 (RALDH2) enzyme is responsible for RA synthesis in the mouse craniofacial region and forebrain between the 8- and 15-somite stages. Raldh2-/- knockout embryos exhibit defective morphogenesis of various forebrain derivatives,including the ventral diencephalon, the optic and telencephalic vesicles. These defects are preceded by regionally decreased cell proliferation in the neuroepithelium, correlating with abnormally low D-cyclin gene expression. Increases in cell death also contribute to the morphological deficiencies at later stages. Molecular analyses reveal abnormally low levels of FGF signaling in the craniofacial region, and impaired sonic hedgehog signaling in the ventral diencephalon. Expression levels of several regulators of diencephalic,telencephalic and optic development therefore cannot be maintained. These results unveil crucial roles of RA during early mouse forebrain development,which may involve the regulation of the expansion of neural progenitor cells through a crosstalk with FGF and sonic hedgehog signaling pathways.

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Section: Ra Deficiency Affects Sonic Hedgehog Signaling In the Forebrainsupporting

confidence: 75%

Retinaldehyde dehydrogenase 2 (RALDH2)-mediated retinoic acid synthesis regulates early mouse embryonic forebrain development by controlling FGF and sonic hedgehog signaling

et al. 2006

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“…2A,B, arrowhead). Further, the Shh-dependent transcription factors, Nkx2.1 and Nkx2.2 (Pabst et al, 2000), which show nested expression domains in the forebrain, were markedly downregulated in Disp1 ∆2/∆2 mutants (Fig. 2E,F,I,J).…”

Section: The Induction Of Shh and Its Targets During Early Forebrain mentioning

confidence: 94%

Dose dependency ofDisp1and genetic interaction betweenDisp1and other hedgehog signaling components in the mouse

2004

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A re-examination within our laboratory of two papers published by our group in Development (Tian et al., 2004; Tian et al., 2005) has revealed a duplication of Dr Tian's data in these papers. On review, we have found that the documentation underpinning a number of conclusions in Tian et al., 2004 is inadequate. As a consequence, we regret that we must retract Tian et al., 2004. The principal conclusions in Tian et al., 2005 are supported by appropriate documentation. Nevertheless, to confirm the conclusions drawn from Dr Tian's primary data on the tissue requirement for Dispatched in facial development, we will repeat the experiments documented in Figure 2 of Tian et al., 2005, and will report our findings to the journal once these experiments have been concluded. We do not expect this re-analysis to change the conclusions drawn in this paper.We apologize to the editors and readership of Development.

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“…Signals produced by axial mesodermal structures, such as Shh and Bmp7, are required to induce Nkx2.1 expression in the neuroepithelium that will give rise to ventral regions of the developing hypothalamus, including the MB (Kimura et al, 1996;Ericson et al, 1995;Pabst et al, 2000). The MB and several ventromedial nuclei of the caudal hypothalamus do not develop in embryos with a loss of Nkx2.1, suggesting that it is required to specify the whole ventrocaudal hypothalamic anlage (Kimura et al, 1996;Marin et al, 2002).…”

Section: Cascade Of Transcription Factors Controlling Mb Developmentmentioning

confidence: 99%

Sim1andSim2are required for the correct targeting of mammillary body axons

et al. 2005

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The mammillary body (MB), and its axonal projections to the thalamus(mammillothalamic tract, MTT) and the tegmentum (mammillotegmental tract,MTEG), are components of a circuit involved in spatial learning. The bHLH-PAS transcription factors SIM1 and SIM2 are co-expressed in the developing MB. We have found that MB neurons are generated and that they survive at least until E18.5 in embryos lacking both Sim1 and Sim2(Sim1-/-;Sim2-/-). However, the MTT and MTEG are histologically absent in Sim1-/-;Sim2-/- embryos, and are reduced in embryos lacking Sim1 but bearing one or two copies of Sim2, indicating a contribution of the latter to the development of MB axons. We have generated, by homologous recombination, a null allele of Sim1 (Sim1tlz) in which the tau-lacZfusion gene was introduced, allowing the staining of MB axons. Consistent with the histological studies, lacZ staining showed that the MTT/MTEG is barely detectable in Sim1tlz/tlz;Sim2+/- and Sim1tlz/tlz;Sim2-/- brains. Instead, MB axons are splayed and grow towards the midline. Slit1 and Slit2,which code for secreted molecules that induce the repulsion of ROBO1-producing axons, are expressed in the midline at the level of the MB, whereas Robo1 is expressed in the developing MB. The expression of Rig-1/Robo3, a negative regulator of Slit signalling, is upregulated in the prospective MB of Sim1/Sim2 double mutants,raising the possibility that the growth of mutant MB axons towards the midline is caused by a decreased sensitivity to SLIT. Finally, we found that Sim1 and Sim2 act along compensatory, but not hierarchical,pathways, suggesting that they play similar roles in vivo.

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NKX2 gene expression in neuroectoderm but not in mesendodermally derived structures depends on sonic hedgehog in mouse embryos

Cited by 90 publications

References 15 publications

Retinaldehyde dehydrogenase 2 (RALDH2)-mediated retinoic acid synthesis regulates early mouse embryonic forebrain development by controlling FGF and sonic hedgehog signaling

Retinaldehyde dehydrogenase 2 (RALDH2)-mediated retinoic acid synthesis regulates early mouse embryonic forebrain development by controlling FGF and sonic hedgehog signaling

Dose dependency ofDisp1and genetic interaction betweenDisp1and other hedgehog signaling components in the mouse

Sim1andSim2are required for the correct targeting of mammillary body axons

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