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Title: Hedgehog Receptor Patched Is Expressed in a Tissue and Gestation Specific Manner During Early Human and Murine Development

Author
item STANFEL, MONIQUE - BAYLOR COLLEGE MED
item BUKOWSKI, JOHN - BAYLOR COLLEGE MED
item SAUTER, AURELIE - BAYLOR COLLEGE MED
item Karpen, Heidi

Submitted to: American Pediatric Society / The Society for Pediatric Research
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2008
Publication Date: 5/1/2008
Citation: Stanfel, M.N., Bukowski, J.T., Sauter, A.A., Karpen, H.E. 2008. Hedgehog receptor Patched is expressed in a tissue and gestation specific manner during early human and murine development [abstract]. American Pediatric Society / The Society for Pediatric Research. E-PAS. 3030.4.

Interpretive Summary:

Technical Abstract: The Hedgehog (Hh) signaling pathway is fundamental for appropriate patterning of nearly every organ system in the developing fetus. The Hh receptor, Patched (Ptc), plays a fundamental role in regulating signal transduction in this pathway. Three main 5 splice forms of the Ptc gene (Ptc1B, Ptc1C, and PtcExon1) have been described, but their significance in embryonic development remains unclear. Alternate splicing of the Hh receptor Ptc leads to tissue and gestation specific expression of receptor isoforms in the developing human and murine embryo. Human embryonic tissue mRNA from 6 to 12 weeks and 26 to 40 weeks gestation was obtained commercially from Genentech, Worcester, MA. QRT-PCR was performed on mRNA from whole human embryo, brain, heart, liver, and lung across these gestational ages and from adult tissues. QRT-PCR was also performed on tissues obtained from timed matings of E7.5-E12.5 CD-1 mice. Ptc isoform expression in adult tissues differs markedly from embryonic tissues. The Ptc1B and Ptc1C isoforms display consistently high expression that is concentrated in the CNS and limbs throughout both early murine and human development. CNS expression appears to be biphasic, while branchial arch and limb expression is sequential. Differential isoform expression is seen in the lung where Ptc 1B and 1C predominate during embryogenesis, while PtcExon1 and 1B are seen at basal levels in the adult. High levels of PtcExon1 are expressed in the yolk sac, heart, and liver, suggesting a contribution to vascular, hematopoietic and mesenchymal differentiation. The individual Ptc isoforms are expressed in unique, overlapping, and sequential manners in both the human and murine embryo. These data suggest that the array and expression of Ptc isoforms, each with differing capacities for pathway regulation in Hh target tissues, may lead to distinct biological activities that function to regulate activation of the Hh signaling pathway leading to graded response essential for patterning. Further work on transcriptional regulation of these isoforms and KO models are needed to determine contribution of individual isoforms to developmental processes suggested here in these studies.