Exam #5: Genetics of Development Flashcards
Regulative Development
Cells are functionally equivalent & loss of a cell can be compensated for resulting in normal development
Mosaic Development
- Occurs after the regulative phase
- A loss of cells cannot be compensated for and will result in abnormal development
Pre-implantation Diagnosis
- Removing a cell in the morula phase i.e prior to implantation, to test for chromosomal aberrations
- Will NOT have a detrimental impact on development
- Regulative phase
What is the first visible axis in the developing embryo?
- Primitive Streak, the groove at which invasion occurs in gastrulation
- Anterior/posterior axis
- Induced by Nodal
Function of the Node
Secrete noggin & chordin to define the dorsal/ ventral axis
Endoderm
- Cells of the gut
- Lung eipthelium
Mesoderm
- Bone
- Muscle
- Internal organs
Ectoderm
- Skin
- Nervous System
What are the three axes in the embryo? What factors regulate their development?
1) Anterior-Posterior (Cranial- Caudal)= Nodal
2) Dorsal-Ventral= Noggin & Chordin
3) Left-Right= Shh
* All are secreted proteins*
Patterning
Division of the embryo into segments to define where the parts will go
HOX
- Transcription Factor with a special DNA binding domain
- Determines patterning along the anterior/posterior axis
What are the five processes by which cells participate in development?
1) Gene regulation by transcription factors & chromatin modification
2) Cell-cell signaling
3) Development of a specific cell shape and polarity
4) Movement & migration of cells
5) Programmed cell death
Malformation
- Result from an intrinsic abnormality in the developmental process
- E.g. polydactyly
Deformation
- Result from an extrinsic influence on the development of an affected tissue
- E.g. Oligohydraminois, or a lack of amniotic fluid that puts constraint on the developing fetus
Disruption
- Destruction of what was an otherwise normal tissue
- E.g. amniotic bands wrapping around fetal limbs & choking off the blood supply (causes amputation)
Sequence
- A cascade of events from an isolated anomaly & leading to multiple malformations
- Phenotypes are caused sequentially by a single defect
- E.g. the Robin Sequence
Syndrome
All of the disease phenotypes are caused by a single defect simultaneously
What is the impact of problems that arise in the first four weeks of development?
- “Blastogenesis”
- Produce major abnormalities that affect entire embryonic regions
- E.g. VACTERL
What is the impact of problems that arise between weeks 5 & 8?
- “Organogenesis”
- Affect single organs and produce single major anomalies
What is the impact of problems that arise after week 8?
- Minor affect on the individual
What are the five most frequent birth defects?
- Heart Defects (1/100-1/200)
- Pyloric Stenosis (1/300)
- Neural Tube Defects (1/1,000)
- Orofacial Clefts (1/700-1/1,000)
- Clubfoot (1,1000)
Situs Inversus
- Developmental defect of the left/right axis
- Internal organs are reversed or mirrored from their normal positions
- Caused by a Shh problem
Situs Ambiguious
- Severe developmental defect of the left/right axis
- Orientation of the internal organs is random
Isolated Anomaly
- Effects a single body region only
- E.g. cleft palate
VACTERL
- Vertebral
- Anal Atresia
- Cardiac
- Tracheo-Esophageal Fistula
- Renal
- Radial Limb Defects
Maternal diabetes is a major risk factors, and the disease is caused by damage to the mesoderm ~20-25 days
What are the most frequent causes of birth defects?
- 50% are multifactorial
- 25% are chromosomal defects
- 20% are single-gene mutations
- 5% are teratogenic
What structure expresses Shh?
Notochord
What initiates left-looping of the heart tube?
Asymmetric expression of Shh, and subsequent left-sided expression of Nodal
Describe the three axes of the developing limb.
1) Shoulder-to-fingertip= proximal-distal
2) Thumb-to-fifth finger= anterior-posterior
3) Dorsum-to-palm= dorsal-ventral
How does the expression of HOX correlate with the structure of the developing embryo?
- Expression correlates with position
- Lower # HOX genes specify structures that are more anterior
Describe the Robin sequence.
- Sequence of events that starts with an isolated anomaly, retardation of mandibular growth
- Displaces the tongue posteriorly
- Prevents closing of the palatal shelves
- Causes a cleft palate
List the five most frequently observed birth defects.
1) Heart Defect
2) Pyloric stenosis
3) Neural tube defects
4) Orofacial clefts
5) Clubfoot
