Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus
The hypothalamus is a region of the anterior forebrain that controls basic aspects of vertebrate physiology, but the genes involved in its development are still poorly understood. Here, we investigate the function of the homeobox gene Rax/Rx in early hypothalamic development using a conditional targ...
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paper:paper_00121606_v416_n1_p212_Orquera2023-06-08T14:35:20Z Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus Rubinstein, Marcelo proopiomelanocortin somatostatin sonic hedgehog protein eye protein homeodomain protein Rax protein, mouse transcription factor animal tissue Article brain development controlled study down regulation embryo embryo development female gene gene expression gene function gene inactivation gene loss hypothalamus morphogenesis mouse nervous system development neuroepithelium nonhuman phenotype priority journal Rax gene Shh gene animal embryology gene expression regulation genetics hypothalamus knockout mouse morphogenesis physiology Animals Body Patterning Embryonic Development Eye Proteins Gene Expression Regulation, Developmental Homeodomain Proteins Hypothalamus Mice Mice, Knockout Transcription Factors The hypothalamus is a region of the anterior forebrain that controls basic aspects of vertebrate physiology, but the genes involved in its development are still poorly understood. Here, we investigate the function of the homeobox gene Rax/Rx in early hypothalamic development using a conditional targeted inactivation strategy in the mouse. We found that lack of Rax expression prior to embryonic day 8.5 (E8.5) caused a general underdevelopment of the hypothalamic neuroepithelium, while inactivation at later timepoints had little effect. The early absence of Rax impaired neurogenesis and prevented the expression of molecular markers of the dorsomedial hypothalamus, including neuropeptides Proopiomelanocortin and Somatostatin. Interestingly, the expression domains of genes expressed in the ventromedial hypothalamus and infundibulum invaded dorsal hypothalamic territory, showing that Rax is needed for the proper dorsoventral patterning of the developing medial hypothalamus. The phenotypes caused by the early loss of Rax are similar to those of eliminating the expression of the morphogen Sonic hedgehog (Shh) specifically from the hypothalamus. Consistent with this similarity in phenotypes, we observed that Shh and Rax are coexpressed in the rostral forebrain at late head fold stages and that loss of Rax caused a downregulation of Shh expression in the dorsomedial portion of the hypothalamus. © 2016 Elsevier Inc. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00121606_v416_n1_p212_Orquera http://hdl.handle.net/20.500.12110/paper_00121606_v416_n1_p212_Orquera |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
proopiomelanocortin somatostatin sonic hedgehog protein eye protein homeodomain protein Rax protein, mouse transcription factor animal tissue Article brain development controlled study down regulation embryo embryo development female gene gene expression gene function gene inactivation gene loss hypothalamus morphogenesis mouse nervous system development neuroepithelium nonhuman phenotype priority journal Rax gene Shh gene animal embryology gene expression regulation genetics hypothalamus knockout mouse morphogenesis physiology Animals Body Patterning Embryonic Development Eye Proteins Gene Expression Regulation, Developmental Homeodomain Proteins Hypothalamus Mice Mice, Knockout Transcription Factors |
| spellingShingle |
proopiomelanocortin somatostatin sonic hedgehog protein eye protein homeodomain protein Rax protein, mouse transcription factor animal tissue Article brain development controlled study down regulation embryo embryo development female gene gene expression gene function gene inactivation gene loss hypothalamus morphogenesis mouse nervous system development neuroepithelium nonhuman phenotype priority journal Rax gene Shh gene animal embryology gene expression regulation genetics hypothalamus knockout mouse morphogenesis physiology Animals Body Patterning Embryonic Development Eye Proteins Gene Expression Regulation, Developmental Homeodomain Proteins Hypothalamus Mice Mice, Knockout Transcription Factors Rubinstein, Marcelo Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus |
| topic_facet |
proopiomelanocortin somatostatin sonic hedgehog protein eye protein homeodomain protein Rax protein, mouse transcription factor animal tissue Article brain development controlled study down regulation embryo embryo development female gene gene expression gene function gene inactivation gene loss hypothalamus morphogenesis mouse nervous system development neuroepithelium nonhuman phenotype priority journal Rax gene Shh gene animal embryology gene expression regulation genetics hypothalamus knockout mouse morphogenesis physiology Animals Body Patterning Embryonic Development Eye Proteins Gene Expression Regulation, Developmental Homeodomain Proteins Hypothalamus Mice Mice, Knockout Transcription Factors |
| description |
The hypothalamus is a region of the anterior forebrain that controls basic aspects of vertebrate physiology, but the genes involved in its development are still poorly understood. Here, we investigate the function of the homeobox gene Rax/Rx in early hypothalamic development using a conditional targeted inactivation strategy in the mouse. We found that lack of Rax expression prior to embryonic day 8.5 (E8.5) caused a general underdevelopment of the hypothalamic neuroepithelium, while inactivation at later timepoints had little effect. The early absence of Rax impaired neurogenesis and prevented the expression of molecular markers of the dorsomedial hypothalamus, including neuropeptides Proopiomelanocortin and Somatostatin. Interestingly, the expression domains of genes expressed in the ventromedial hypothalamus and infundibulum invaded dorsal hypothalamic territory, showing that Rax is needed for the proper dorsoventral patterning of the developing medial hypothalamus. The phenotypes caused by the early loss of Rax are similar to those of eliminating the expression of the morphogen Sonic hedgehog (Shh) specifically from the hypothalamus. Consistent with this similarity in phenotypes, we observed that Shh and Rax are coexpressed in the rostral forebrain at late head fold stages and that loss of Rax caused a downregulation of Shh expression in the dorsomedial portion of the hypothalamus. © 2016 Elsevier Inc. |
| author |
Rubinstein, Marcelo |
| author_facet |
Rubinstein, Marcelo |
| author_sort |
Rubinstein, Marcelo |
| title |
Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus |
| title_short |
Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus |
| title_full |
Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus |
| title_fullStr |
Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus |
| title_full_unstemmed |
Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus |
| title_sort |
essential function of the transcription factor rax in the early patterning of the mammalian hypothalamus |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00121606_v416_n1_p212_Orquera http://hdl.handle.net/20.500.12110/paper_00121606_v416_n1_p212_Orquera |
| work_keys_str_mv |
AT rubinsteinmarcelo essentialfunctionofthetranscriptionfactorraxintheearlypatterningofthemammalianhypothalamus |
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