Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 676

and after placental transfer in embryos. 3 Retinoic acid controls the activity of
fibroblast growth factor and sonic Hedgehog [ 1387 ].
Among transcription factors expressed predominantly in the heart, members
of the GATA set — GATA4, GATA5, and GATA6 — require vitamin-A [ 1386 ].
Retinoid-regulated cardiogenesis also involves transcription factor of the Msh
homeobox class Msx1 that also needs vitamin-A input. Cardiac abnormalities result
from lack or excess of retinoids.
Specification of any embryonic cell lineage is controlled by the sum of activities
of transcription factors — activators and repressors — that result from interactions
between involved genes that encode these transcription factors following a given
signaling. Many genes indeed participate in specification and differentiation of
embryonic cell lineages and progressive organization of tissues and organs. De-
velopment genes coordinate the sequence of interactions between genes that encode
transcription and signaling factors.
Long and small non-coding RNAs (ncRNAs) regulate organogenesis [ 1388 ].
Small ncRNAs are associated with heterochromatin formation via the RNA interfer-
ence pathway. Long ncRNAs are linked to gene clusters. Non-coding RNAs regulate
transcription, as they interact with transcription factors, RNA polymerases, or DNA.
Short interspersed elements of the genome transcribe non-coding RNAs that repress
specific genes by binding to and inhibiting RNA polymerase-2.
The cell's capacity to differentiate with specialized attributes is, at least partially,
achieved using the genetic code. In the large majority of cases, cells acquire their
fate owing to their lineage or signaling from adjoining cell lineages. In addition to
the deterministic program, the differentiation pathway can be randomly fullfilled to
cope with adverse changes in the environment [ 1389 ].
Cells interact with adjoining cells and the extracellular matrix owing to cell
adhesion molecules such as integrins that serve as receptors of matrix constituents.
Cell adhesion molecules link intracellular cytoskeletal proteins of adjacent cells as
well as cytoskeleton to matrix constituents. Matrix constituents influence intracel-
lular events via their receptors that lodge at the cell surface, thereby modulating
cell differentiation, migration, and polarization. In addition, cells release matrix-
degrading enzymes and their inhibitors to remodel their nearby environment.
In kidney genesis, epithelial-mesenchymal interactions require connections of
α 8 β 1 -integrins to extracellular matrix protein nephronectin [ 1390 ]. Nephronectin
3 Retinol is taken up by retinol-binding protein (RBP), transferred into cells by the receptor protein
stimulated by retinoic acid STRA6, and transformed into retinaldehyde by cytosolic alcohol
dehydrogenases (ADH) and microsomal retinol dehydrogenases (RDH). Retinol to retinaldehyde
conversion is catalyzed mainly by retinol dehydrogenase RDH10 (canonical synthesis). The final
step is the oxidation of retinaldehyde into retinoic acid. Retinoic acid is synthesized by reti-
naldehyde dehydrogenases (RALDH1-RALDH3) and a group of cytochrome-P450s (CyP26a1-
CyP26c1) with tissue specificity. In addition, β -carotene cleavage by β -carotene dioxygenase
generates retinaldehyde (alternative synthesis). Cellular retinol-binding proteins (CRBP) and
retinoic acid-binding proteins (CRABP) participate in retinoic acid acitivity.