CBP/p300 and associated transcriptional co-activators exhibit distinct expression patterns during murine craniofacial and neural tube development.
Mutations in each of the transcriptional co-activator genes - CBP, p300, Cited2, Cart1 and Carm1 - result in neural tube defects in mice. The present study thus furnishes a complete and comparative temporal and spatial expression map of CBP/p300 and associated transcriptional co-activators, Cited2, Cart1 and Carm1 during the period of murine neural tube development (embryonic days 8.5 to 10.5). Each co-activator except Cart1 was expressed in the dorsal neural folds on E8.5. Although CBP and p300 are functionally interchangeable in vitro, their respective expression patterns diverge during embryogenesis before neural fold fusion is complete. CBP gene expression was lost from the neural folds by E8.75 and was thereafter weakly expressed in the maxillary region and limb buds, while p300 exhibited strong expression in the first branchial arch, limb bud and telencephalic regions on E9.5. Cart1 exhibited strong expression in the forebrain mesenchyme from E9.0 through E10.5. Although CBP, p300, Carm1 and Cited2 share temporal expression on E8.5, these co-activators have different spatial expression in mesenchyme and/or the neuroepithelium. Nevertheless, co-localization to the dorsal neural folds on E8.5 suggests a functional role in elevation and/or fusion of the neural folds. Target genes, and pathways that promote cranial neural tube fusion that are activated by CBP/p300/Carm1/Cited2/Cart1-containing transcriptional complexes await elucidation.
Bhattacherjee
Vasker
V
University of Louisville Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, ULSD, KY 40292, USA.
Horn
Kristin H
KH
Singh
Saurabh
S
Webb
Cynthia L
CL
Pisano
M Michele
MM
Greene
Robert M
RM
D000818:Animals; D001483:Base Sequence; D050882:CREB-Binding Protein / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000235:genetics; D005147:Facial Bones / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D018398:Homeodomain Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008813:Mice, Inbred ICR; D054259:Neural Tube / Q000196:embryology* / Q000378:metabolism*; D011247:Pregnancy; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012886:Skull / Q000196:embryology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics; D050880:p300-CBP Transcription Factors / Q000235:genetics* / Q000378:metabolism
C489986:Alx1 protein, mouse; C110087:Cited2 protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D050880:p300-CBP Transcription Factors