Cleft Palate Developmental Biology
Palatal development begins with the induction and organization of primitive neuroectodermal structures. As the germ layers form, mesenchyme flows from these organizing elements through the primitive streak, pouring the foundation for the craniofacial primordia. The ectoderm then infuses neural crest cells into the frontonasal region causing the medial nasal, lateral nasal and maxillary prominences to thicken and collide. Fusion of these prominences obliterates the intervening epithelium and amalgamates the mesenchyme. Ultimately, the assembly of these amorphous craniofacial primordia produces seamless primary and secondary palatal structures. If the timing, rate, or extent of these morphogenetic movements is interrupted, the primordia fail to fuse and a cleft in the lip, palate or midface develops. Since the embryopathogenesis of primary and secondary palate formation is extremely complex, we have established an in vitro murine palate organ culture model. This model has enabled us to define a critical distance for cleft palate formation in vitro and we have successfully treated this in vitro cleft with mesenchymal stem cell therapy. In addition to our mouse model, we are also investigating zebra fish palate development.
Selected Articles:
Erfani S, Maldonado TS, Crisera CA, Warren SM, Lee S, Longaker MT.
An in vitro mouse model of cleft palate: defining a critical intershelf distance necessary for palatal clefting. Plast Reconstr Surg. 2001 Aug;108(2):403-10.
Lee S, Crisera CA, Erfani S, Maldonado TS, Lee JJ, Alkasab SL, Longaker MT. Immunolocalization of fibroblast growth factor receptors 1 and 2 in mouse palate development. Plast Reconstr Surg. 2001 Jun;107(7):1776-84; discussion 1785-6.
Lorenz HP, Hedrick MH, Chang J, Mehrara BJ, Longaker MT. The impact of biomolecular medicine and tissue engineering on plastic surgery in the 21st century.
Plast Reconstr Surg. 2000 Jun;105(7):2467-81.
Stelnicki EJ, Lee S, Hoffman W, Lopoo J, Foster R, Harrison MR, Longaker MT.A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model. Plast Reconstr Surg. 1999 Sep;104(3):607-15.
Levine JP, Bradley JP, Shahinian HK, Longaker MT. Nasal expansion in the fetal lamb: a first step toward management of cleft nasal deformity in utero. Plast Reconstr Surg. 1999 Mar;103(3):761-7.
Stelnicki EJ, Hoffman W, Foster R, Lopoo J, Longaker M. The in utero repair of Tessier number 7 lateral facial clefts created by amniotic band-like compression. J Craniofac Surg. 1998 Nov;9(6):557-62; discussion 563.
Lopoo JB, Hedrick MH, Chasen S, Montgomery L, Chervenak FA, Goldstein R, Hoffman WY, Harrison MR, Longaker MT. Natural history of fetuses with cleft lip. Plast Reconstr Surg. 1999 Jan;103(1):34-8.
Stelnicki EJ, Vanderwall K, Hoffman WY, Szabo Z, Harrison MR, Foster R, Longaker MT. Adverse outcomes following endoscopic repair of a fetal cleft lip using an ovine model. Cleft Palate Craniofac J. 1998 Sep;35(5):425-9.
Stelnicki EJ, Hoffman WY, Vanderwall K, Harrison MR, Foster R, Longaker MT. A new in utero model for lateral facial clefts. J Craniofac Surg. 1997 Nov;8(6):460-5.
Hedrick MH, Rice HE, Vander Wall KJ, Adzick NS, Harrison MR, Siebert J, Hoffman WY, Longaker MT. Delayed in utero repair of surgically created fetal cleft lip and palate. Plast Reconstr Surg. 1996 Apr;97(5):900-5; discussion 906-7.
Longaker MT, Stern M, Lorenz P, Whitby DJ, Dodson TB, Harrison MR, Adzick NS, Kaban LB. A model for fetal cleft lip repair in lambs. Plast Reconstr Surg. 1992 Nov;90(5):750-6.
