Genetics of Development Flashcards
Regulative Phase
- -first phase of development
- -loss of a cell will not hurt the embryo (neighboring cells will compensate)
- -cells are functionally equivalent
- -
Embryonal Period
–week 1-8
Implantation occurs at?
–day 7-12 after fertilization
Mosaic Phase
- -loss of a cell cannont be compensated for
- -leads to loss of part of tissue for whatever that cell was going to contribute to
- defects in mosaic phase can lead to birth defects
Phases of Development
- -regulative
- -mosaic
- -axis formation
3 Axes that need to be defined
- -head to toe (cranial-caudal)
- -dorsal-ventral
- -left-right
First Visible Structure in embryo
- -anterior/posterior axis
- -defined by primitive streak
Primitive Streak/Anterior-Posterior development
- -marks the groove at which ectodermal cells invade into the space between epiblast and hypoblast to form separate germ layer
- -gene called nodal is required for formation of primitive streak
- -anterior end of streak is the node
Dorsal Ventral Development
- -induced by gene products of noggin and chordin genes
- -concentration dependent manner (gradient)
Left-Right Asymmetry
- -causes by asymmetric expression of Shh gene from notochord
- -sinus inversus (organs on opposite side of body they should be)
- -Shh also used in concentration dependent manner
Patterning
- -occurs after axes have been established
- -Hox genes encode DNA homeobox binding transcription factors
- -each tissue expresses different combo of hox genes depending on location of that specific tissue
Hox genes
- -used in patterning development
- -transcription factors
- -expressed in response to morphagens (nodol, noggin, Shh, chordin)
- -4 Classes HoxA-D
- -13 members of each class
- -larger numbers deal with cells/tissues more distal (think pinky finger would be like HoxD-13)
5 Mechanisms operating at cellular level during development
- -gene regulation by transcription factors
- -cell-cell signaling (by direct contact or secretion of morphogens)
- -development of specific cell shape and polarity
- -movement and migration of cells
- -programmed cell death or apoptosis
Cause of Defect described by what terms?
- -malformation
- -deformation
- -disruption
mechanism by which one defect causes multiple abnormalities is described by?
–sequence and syndrome
Malformation
- -result from an intrinsic abnormality in the developmental process
- -ex. polydactyly
- -originate from defect within affected organ
Deformations
- -results from extrinsic influence on development of affected tissue
- -ex. oligohydraminos (lack of amniotic fluid–causes constraint on development fetus–no room to expand)
Disruptions
- -result from destruction of developing tissue
- -ex. amniotic bands–wrap around developing tissue, cut off blood supply, killing tissue
Isolated Anomalies
- -ex. cleft palate
- -affect single body region
- -sporadic or multifactorial
- -60% of major birth defects are
Sequence
- -cascade of events starting from a single isolated anomaly and leading to multiple malformations
- -sequences are usually sporadic or multifactorial
- -disease phenotypes are present sequentially
Syndrome
- -when all disease phenotypes are caused by a single defect
- -affects several body regions and most often display chromosomal or mendelian inheritance
Robin Sequence
- -series of events that starts w/ retardation of mandibular growth (due to variety of different possible defects; see slide)
- -displaces tongue posteriorly and prevents closing of palatal shelves
Damage of Embryo Weeks 1-4
- -blastogenesis
- -multiple major abnormalities in entire embryonic regions
- -ex. VACTRL
Damage of Embryo Weeks 5-8
- -organogenesis
- -abnormalities in specific organs, single major anomalies
- -ex. congenital heart defects
Damage after week 9
- -after organ formation
- -mild effects
- -ex. presence of single palmar crease
VACTERL
- -vertebral, anal atresia, cardiac, tracheo-esophagal fistula, renal and radial limb defects
- -weeks 1-4
- -maternal diabetes is risk factor
Rate of Children Born w/ birth defect
–2-3%
Most Common Birth Defects and their prevalences
- -heart defects: 1/100-200 live births
- -pyloric stenosis: 1/300
- -neural tube defects: 1/1,000
- -orofacial clefts: 1/700-1,000
- -clubfoot: 1/1,000
Birth defects account for % of infant mortality (% if premature births included)
- -20% infant mortality
- -40% w/ premature births
Inheritance of genetic defects that cause birth defects
- -50% have complex inheritance
- -25% are caused by chromosomal defects
- -25% are caused by single gene mutations
- -in only about 5% of cases, the malformation can be traced to non-genetic factors (smoking, drinking, drugs, maternal meds and infections)
Development is…? (2 general characteristics)
- -tightly regulated: even one additional cell division during early development is likely fatal; extra division in late development may give segmental growth
- -Extremely robust: disturbances to normal developmental process occur regularly; these are countered by regulatory mechanisms
Genetically similar mice in same environment have mutation of foramin
- -only 20% have renal defects
- -shows that lots of development is left up to chance
