Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations

Tian Yang; Zhonglin Jia; Whitney Bryant‐Pike; Anand Chandrasekhar; Jeffrey C Murray; Bernd Fritzsch; Alexander G Bassuk

doi:10.1002/mgg3.53

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Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations

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Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations

Tian Yang, Zhonglin Jia, Whitney Bryant‐Pike, Anand Chandrasekhar, Jeffrey C Murray, Bernd Fritzsch and Alexander G Bassuk

Molecular genetics & genomic medicine, Vol.2(2), pp.138-151

03/2014

DOI: 10.1002/mgg3.53

PMCID: PMC3960056

PMID: 24689077

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Abstract

Palate development is shaped by multiple molecular signaling pathways, including the Wnt pathway. In mice and humans, mutations in both the canonical and noncanonical arms of the Wnt pathway manifest as cleft palate, one of the most common human birth defects. Like the palate, numerous studies also link different Wnt signaling perturbations to varying degrees of limb malformation; for example, shortened limbs form in mutations of Ror2, Vangl2looptail and, in particular, Wnt5a. We recently showed the noncanonical Wnt/planar cell polarity (PCP) signaling molecule Prickle1 (Prickle like 1) also stunts limb growth in mice. We now expanded these studies to the palate and show that Prickle1 is also required for palate development, like Wnt5a and Ror2. Unlike in the limb, the Vangl2looptail mutation only aggravates palate defects caused by other mutations. We screened Filipino cleft palate patients and found PRICKLE1 variants, both common and rare, at an elevated frequency. Our results reveal that in mice and humans PRICKLE1 directs palate morphogenesis; our results also uncouple Prickle1 function from Vangl2 function. Together, these findings suggest mouse and human palate development is guided by PCP‐Prickle1 signaling that is probably not downstream of Vangl2. We show Prickle1 mutation in mice causes complete cleft palate; PRICKLE1 variants in humans are associated with cleft palate. Our findings support Prickle1 is part of Wnt/PCP signaling, which does not require Vangl2 during palate development.

Vangl2

Cleft palate

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Prickle1

Details

Title: Subtitle: Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates rare and common variants involved in human malformations
Creators: Tian Yang - University of Iowa
Zhonglin Jia - Sichuan University
Whitney Bryant‐Pike - University of Missouri
Anand Chandrasekhar - University of Missouri
Jeffrey C Murray - University of Iowa
Bernd Fritzsch - University of Iowa
Alexander G Bassuk - University of Iowa
Resource Type: Journal article
Publication Details: Molecular genetics & genomic medicine, Vol.2(2), pp.138-151
DOI: 10.1002/mgg3.53
PMID: 24689077
PMCID: PMC3960056
NLM abbreviation: Mol Genet Genomic Med
ISSN: 2324-9269
eISSN: 2324-9269
Number of pages: 14
Grant note: National Institutes of Health (NIH) (R01 DC005590; P30 DC 010362; NS040449; DE08559; 1R01 NS064159‐01A1)
Language: English
Date published: 03/2014
Academic Unit: Neurology; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Iowa Neuroscience Institute; Biology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Neurology (Pediatrics); Dental Research
Record Identifier: 9984014022202771

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