The etiology of cleft palate: a 50‐year search for mechanistic and molecular understanding

Abstract

Dates of special, historical significance, such as the 50th anniversary of the founding of the Teratology Society, prompt a desire to pause and look back and contemplate where we began, how far we have come, and consider the future for our scientific endeavors. The study of the etiology of cleft palate extends many years into the past and was a subject of interest to many of the founding members of the Teratology Society. This research area was intensively pursued and spawned a vast portfolio of published research. This article will look back at the state of the science around the time of the founding of the Teratology Society, in the 1950s and 1960s, and track the emergence and pursuit of an interest in an etiology for cleft palate involving failure of palatal fusion. Studies of medial epithelial cell fate and induction of cleft palate by interference with adhesion or fusion span the period from the 1960s to the present time. Teratology Society members have been and continue to be key players in cleft palate research. In this retrospective article, seminal research published by Teratology Society members will serve as a platform to launch the discussion of the emergence of our current understanding of medial epithelial cell differentiation and fate and the potential for these processes to be targets of teratogenic action.

Genetics of cleft lip and cleft palate

“…Other nutrients, including cholesterol [Porter, 2006], zinc [Munger et al, 2009], and general multivitamin use [Johnson and Little 2008] have also been studied, but need to be expanded to larger populations. Finally, other exposures to teratogens and environmental toxins have also been associated with increased risk of clefting [Abbott, 2010] such as retinoic acid, valproic acid, and phenytoin. A more comprehensive review of environmental risk factors for orofacial clefts is provided by Rahimov et al [2012] and Vieira [2012].…”

Development of an organotypic stem cell model for the study of human embryonic palatal fusion

“…While CP can result from an aberration of any of the processes that form the palate, it can also result from failure of the fusion event alone. The etiology of this malformation involves multiple genetic and environmental factors (Abbott, ; Cobourne, ; Murray & Schutte, ) although all the etiological pathways have not yet been elucidated. Study of CP has traditionally been performed with animal models in vivo or with nonhuman organ culture in vitro.…”

Mechanisms of tissue fusion during development

“…Importantly, the inability of tissues to fuse correctly during development can lead to various birth defects, including cleft palate (Abbott, 2010), spina bifida (Copp et al, 1990) and heart defects (Wenink and Zevallos, 1988). The etiology of these debilitating defects in humans is likely to be complex, involving the concurrent disruption of several factors.…”