In vivo functional analysis of the Hoxa-1 3' retinoic acid response element (3'RARE) - PubMed (original) (raw)
. 1997 Jan;124(2):399-410.
doi: 10.1242/dev.124.2.399.
Affiliations
- PMID: 9053316
- DOI: 10.1242/dev.124.2.399
In vivo functional analysis of the Hoxa-1 3' retinoic acid response element (3'RARE)
V Dupé et al. Development. 1997 Jan.
Abstract
Retinoids are essential for normal development and both deficiency and excess of retinoic acid (RA) are teratogenic. Retinoic acid response elements (RAREs) have been identified in Hox gene promoters suggesting that endogenous retinoids may be involved in the direct control of Hox gene patterning functions. In order to test this hypothesis, we have mutated the Hoxa-1 3'RARE using the Cre-loxP targeting strategy, and studied its functional role during mouse development. We find that this enhancer plays an important role in the early establishment of the Hoxa-1 anterior expression boundary in the neural plate. This early disturbance in Hoxa-1 activation results in rhombomere and cranial nerve abnormalities reminiscent of those obtained in the Hoxa-1 total knockout, although their severity and penetrance are lower, thus providing strong evidence for direct control of Hox gene function by retinoids during normal development. Interestingly, we also find that the Hoxa-1 expression response to RA treatment is not entirely controlled by the RARE, suggesting the existence of other retinoid-induced factors mediating the Hoxa-1 response to RA and/or the presence of additional RAREs. Interestingly, although the RARE is not required for the spatiotemporal control of colinear expression of the Hoxa genes, it is absolutely required for correct Hoxa-2 expression in rhombomere 5.
Similar articles
- Evolutionary-conserved enhancers direct region-specific expression of the murine Hoxa-1 and Hoxa-2 loci in both mice and Drosophila.
Frasch M, Chen X, Lufkin T. Frasch M, et al. Development. 1995 Apr;121(4):957-74. doi: 10.1242/dev.121.4.957. Development. 1995. PMID: 7743939 - Long-range regulation by shared retinoic acid response elements modulates dynamic expression of posterior Hoxb genes in CNS development.
Ahn Y, Mullan HE, Krumlauf R. Ahn Y, et al. Dev Biol. 2014 Apr 1;388(1):134-44. doi: 10.1016/j.ydbio.2014.01.027. Epub 2014 Feb 10. Dev Biol. 2014. PMID: 24525295 - A conserved enhancer of the human and murine Hoxa-7 gene specifies the anterior boundary of expression during embryonal development.
Knittel T, Kessel M, Kim MH, Gruss P. Knittel T, et al. Development. 1995 Apr;121(4):1077-88. doi: 10.1242/dev.121.4.1077. Development. 1995. PMID: 7538068 - Retinoids and Hox genes.
Marshall H, Morrison A, Studer M, Pöpperl H, Krumlauf R. Marshall H, et al. FASEB J. 1996 Jul;10(9):969-78. FASEB J. 1996. PMID: 8801179 Review. - Retinoic acid and homeobox gene regulation.
Langston AW, Gudas LJ. Langston AW, et al. Curr Opin Genet Dev. 1994 Aug;4(4):550-5. doi: 10.1016/0959-437x(94)90071-a. Curr Opin Genet Dev. 1994. PMID: 7950323 Review.
Cited by
- A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment.
Abraham E, Volmert B, Roule T, Huang L, Yu J, Williams AE, Cohen HM, Douglas A, Megill E, Morris A, Stronati E, Fueyo R, Zubillaga M, Elrod JW, Akizu N, Aguirre A, Estaras C. Abraham E, et al. bioRxiv [Preprint]. 2024 Jul 12:2024.07.11.602981. doi: 10.1101/2024.07.11.602981. bioRxiv. 2024. PMID: 39026825 Free PMC article. Preprint. - Genetically programmed retinoic acid deficiency during gastrulation phenocopies most known developmental defects due to acute prenatal alcohol exposure in FASD.
Petrelli B, Oztürk A, Pind M, Ayele H, Fainsod A, Hicks GG. Petrelli B, et al. Front Cell Dev Biol. 2023 Jun 16;11:1208279. doi: 10.3389/fcell.2023.1208279. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37397253 Free PMC article. - Spinal Cord Organoids to Study Motor Neuron Development and Disease.
Buchner F, Dokuzluoglu Z, Grass T, Rodriguez-Muela N. Buchner F, et al. Life (Basel). 2023 May 25;13(6):1254. doi: 10.3390/life13061254. Life (Basel). 2023. PMID: 37374039 Free PMC article. Review. - Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube.
Afzal Z, Lange JJ, Nolte C, McKinney S, Wood C, Paulson A, De Kumar B, Unruh J, Slaughter BD, Krumlauf R. Afzal Z, et al. Development. 2023 May 15;150(10):dev201259. doi: 10.1242/dev.201259. Epub 2023 May 24. Development. 2023. PMID: 37102683 Free PMC article. - BRCA1 and TP53 codeficiency causes a PARP inhibitor-sensitive erythroproliferative neoplasm.
Lopez-Perez G, Wijayatunge R, McCrum KB, Holmstrom SR, Mgbemena VE, Ross TS. Lopez-Perez G, et al. JCI Insight. 2022 Dec 22;7(24):e158257. doi: 10.1172/jci.insight.158257. JCI Insight. 2022. PMID: 36346676 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous