D. Macias et al., IN-VIVO INHIBITION OF PROGRAMMED CELL-DEATH BY LOCAL-ADMINISTRATION OF FGF-2 AND FGF-4 IN THE INTERDIGITAL AREAS OF THE EMBRYONIC CHICK LEGBUD, Anatomy and embryology, 193(6), 1996, pp. 533-541
The formation of the digits in amniote vertebrates is accompanied by a
massive degeneration process that accounts for the disappearance of t
he interdigital mesenchyme. The establishment of these areas of interd
igital cell death (INZs) is concomitant with the flattening of the api
cal ectodermal ridge (AER), but a possible causal relationship between
these processes has not been demonstrated. Recent studies have shown
that the function of the AER can be substituted for by implantation of
beads bearing either FGF-2 or FGF-4 into the apical mesoderm of the e
arly limb bud. According to these observations, if the onset of INZs i
s triggered by the cessation of the AER function, local administration
of FGFs to the interdigital tissue prior to cell death should delay o
r inhibit interdigit degeneration. In the present study we have confir
med this prediction. Implanting Affi-gel blue or heparin beads pre-abs
orbed with either FGF-2 or FGF-4 into the interdigital tissue of the c
hick leg bud in the stages prior to cell death stimulates cell prolife
ration and causes the formation of webbed digits. Vital staining with
neutral red confirmed an intense temporal inhibition of interdigital c
ell death after FGF treatment. This inhibition of interdigital cell de
ath was not accompanied by modifications in the pattern of expression
of Msx-1 or Msx-2 genes, which in normal development display a domain
of expression in the interdigital tissue preceding the onset of degene
ration.