PMID- 9672841
OWN - NLM
STAT- MEDLINE
DCOM- 19981005
LR  - 20131121
IS  - 0270-4145 (Print)
IS  - 0270-4145 (Linking)
VI  - 18
IP  - 2
DP  - 1998 Apr-Jun
TI  - Mesenchymal changes associated with retinoic acid induced cleft palate in CD-1 
      mice.
PG  - 88-99
AB  - Retinoic acid (RA) is teratogenic in many species and is an effective inducer of 
      cleft palate in mice. The pathogenesis of cleft formation varies with the timing 
      of exposure. It has been demonstrated, before formation of the palatal shelves, 
      that RA exposure results in insufficient mesenchymal tissue, and palatal shelves 
      fail to make contact. However, at the palatal shelf outgrowth stage, RA exposure 
      affects shelf elevation and growth in rats, and possibly medial edge epithelium 
      (MEE) differentiation in mice. The objective of this study was to examine the 
      morphologic and functional changes associated with cleft formation in mice 
      following exposure during shelf outgrowth. Particular emphasis was placed on 
      evaluating the timing of palatal shelf elevation in RA exposed embryos and on 
      identifying differentiation events occurring concurrently in the epithelium. On 
      gestational day (GD) 12 (8:00 AM), gravid CD-1 mice were gavaged with 70 mg/kg RA 
      or vehicle. This protocol produced a 100% incidence of cleft palate at term, 
      allowing us to correlate the morphological and/or biochemical changes observed at 
      pre-fusion time points. Embryos were collected at 12 hr intervals through GD 15, 
      beginning 4 hr after exposure. Serial sections of embryos were either stained 
      with H&E, with a battery of lectins [Sambucus nigra (SNA), Arachis hypogaea 
      (PNA), Ricinus communis (RCA-1), Glycine max (SBA), Succinylated Wheat Germ 
      (S-WGA)], or with a probe to hyaluronan. Throughout the period of normal palate 
      development, the shelf mesenchyme showed increasing regional organization and 
      progressive hydration and these changes were correlated with increase Hyaluronan 
      (HA) deposition. RA treatment resulted in lose of regional organization and 
      delayed mesenchyme hydration. In association with these changes there were 
      reductions in HA deposition and extracellular matrix glycoconjugates recognized 
      by PNA in the palate mesenchyme. Further there was a considerable delay in 
      palatal shelf elevation and palate shelf did not make contact at the midline. Our 
      data indicates, in embryos exposed on GD 12 to levels of RA sufficient to induce 
      a 100% incidence of clefting, that cleft formation is a result of palatal shelves 
      failing to make contact. Alterations in mesenchyme development and the subsequent 
      delay in palate shelve elevation are central to RA-induced cleft formation 
      following exposure at the palate shelf out growth stage.
FAU - Degitz, S J
AU  - Degitz SJ
AD  - Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign 
      61801, USA.
FAU - Francis, B M
AU  - Francis BM
FAU - Foley, G L
AU  - Foley GL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Denmark
TA  - J Craniofac Genet Dev Biol
JT  - Journal of craniofacial genetics and developmental biology
JID - 8109845
RN  - 0 (Peanut Agglutinin)
RN  - 0 (Teratogens)
RN  - 5688UTC01R (Tretinoin)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Animals
MH  - Cleft Palate/*chemically induced
MH  - Female
MH  - Histocytochemistry
MH  - Hyaluronic Acid
MH  - Mesoderm/*drug effects/pathology
MH  - Mice
MH  - Peanut Agglutinin
MH  - Pregnancy
MH  - Teratogens/*toxicity
MH  - Tretinoin/*toxicity
EDAT- 1998/07/22 00:00
MHDA- 1998/07/22 00:01
CRDT- 1998/07/22 00:00
PHST- 1998/07/22 00:00 [pubmed]
PHST- 1998/07/22 00:01 [medline]
PHST- 1998/07/22 00:00 [entrez]
PST - ppublish
SO  - J Craniofac Genet Dev Biol. 1998 Apr-Jun;18(2):88-99.