The hedgehog pathway is extremely important in vertebrate limb development, neural differentiation and facial morpho-genesis. In accordance with the above statement, what would happen in mice that are homozygous for a mutant allele of sonic hedgehog (shh)?
Midline of the face would be reduced and a single eye would form in the center of the forehead.
Sonic Hedgehog Pathway and Development
The question discusses the critical role of the hedgehog pathway, specifically focusing on sonic hedgehog (shh), in vertebrate development. This pathway is essential for patterning and growth during embryogenesis, including the formation of limbs, the nervous system, and facial structures.
Role of Sonic Hedgehog (Shh) in Facial Development
Sonic hedgehog (Shh) is a signaling protein that acts as a morphogen, meaning it directs the fate of cells based on its concentration. In facial development, Shh signaling is crucial for establishing the midline structures. It is particularly important for the division of the forebrain and the proper separation of the two eyes.
When sonic hedgehog signaling is impaired, particularly in the forebrain, it can lead to a severe condition known as holoprosencephaly. This condition involves incomplete separation of the forebrain hemispheres and associated facial malformations.
Consequences of Mutant shh Allele in Mice
Mice that are homozygous for a mutant allele of sonic hedgehog (shh) have significantly disrupted Shh signaling. Since Shh is vital for midline patterning during facial development, a severe reduction or absence of functional Shh protein in these mice results in severe midline defects.
The most prominent and severe consequence of lacking functional sonic hedgehog in early development, as observed in homozygous shh mutant mice, is cyclopia. This is a type of holoprosencephaly where the midline of the face is severely reduced, and the two eyes fail to separate, resulting in the formation of a single, central eye in the forehead.
Analyzing the Options
- Limbs would form normally but the mice would have facial abnormalities.
- While sonic hedgehog is crucial for facial development, it is also fundamentally important for limb patterning (specifically, establishing the anterior-posterior axis of the limb). Therefore, homozygous shh mutants would likely have severe limb defects as well, not normal limbs. So, this option is unlikely.
- Midline of the face would be reduced and a single eye would form in the center of the forehead.
- This describes cyclopia, a well-documented severe phenotype of homozygous sonic hedgehog mutations in mice and other vertebrates due to the failure of forebrain and facial midline development. This aligns with the known function of Shh.
- Eyes would form normally but digits would be malformed.
- As discussed, sonic hedgehog is critical for eye separation and facial midline formation. Normal eye formation is highly improbable in the absence of Shh signaling. While digit malformations (polydactyly or syndactyly, depending on the specific mutation and context) can occur with hedgehog pathway disruptions, normal eyes would contradict the primary role of Shh in forebrain and facial development. So, this option is unlikely.
- Mutations of shh may activate tumor formation if Patched protein can inhibit the Smoothened protein.
- This option describes the mechanism by which activating mutations in the pathway components (like Patched or Smoothened) can lead to tumor formation (e.g., medulloblastoma, basal cell carcinoma) because unregulated Smoothened activates the pathway inappropriately. However, the question describes a mutant allele of shh, implying a loss-of-function mutation (homozygous implies severe loss). A loss-of-function shh mutation would typically lead to developmental defects due to insufficient signaling, not tumor formation due to activated signaling. Tumor formation linked to the hedgehog pathway usually involves activating mutations in downstream components or loss of inhibitors like Patched.
Based on the known severe developmental roles of sonic hedgehog, particularly in midline patterning of the face and forebrain, the phenotype described in option 2 is the most accurate outcome for mice homozygous for a loss-of-function shh mutant allele.
Important Questions from Morphogenesis and organogenesis in animals
A "morphogen" can determine the fate of a cell by its concentration. Given below are some statements on the experiment performed to study the gradient-dependent effect of the morphogen, activin on cell fate by placing activin (4 nm)-secreting beads on unspecified cells from an early Xenopus embryo:
A. Beads without activin did not elicit expression of either Xbra or goosecoid genes.
B. Cells nearest to the beads getting highest concentration of activin induced goosecoid gene whose product is a transcription factor, specifies the frog's dorsal-most structures.
C. Cells nearest to the beads getting highest concentration of activin induced Xbra gene whose product is a transcription factor, specifies the frog's dorsal-most structures.
D. Cells farthest from the beads getting negligible activin activate Xbra gene and become blood vessels and heart.
E. Cells farthest from the beads getting negligible activin, activated neither Xbra nor goosecoid and the 'default' gene expression instructed the cells to become blood vessels and heart.
Which of the above observations and conclusions drawn are correct?
The individuals considered in this question are having two haploid sets of autosomes and no Y- chromosome. The X∶A ratio of the individuals, the type of organisms chosen, their primary sex and number of Barr bodies expected in their cells are shown in the table below:
X∶A ratio Organism Primary Sex Number of Barr bodies i. 0.5
ii. 2
A. Human
B. Drosophila
I. Male
II. Female
III. Metafemale
a. Zero
b. One
c. Two
d. Three
Select the option below with all correct matches:
Several marine organism release their gametes into the environment, where sperm attraction and subsequent events lead to successful fertilization. With reference to sea urchins, which one of the following statements is NOT true?
The following statements regarding the generation of dorsal/ventral axis in Drosophila was made:
A. Gurken protein moves along with the oocyte nucleus and signals follicle cells to adopt the ventral fate.
B. Maternal deficiencies of either the gurken or torpedo gene cause ventralization of the embryo.
C. Gurken is active only in the oocyte and Torpedo is active only in the somatic follicle cells.
D. The Pipe protein is made in the dorsal follicle cells.
E. The highest concentration of Dorsal is in the dorsal cell nuclei, which becomes the mesoderm.
Which one of the following combination of the above statements is true?
During wing development in chick, if Apical Ectodermal Ridge (AER) is removed, the limb development ceases, on the other hand placing leg mesenchyme directly beneath the wing AER, distal hindlimb structures develop at the end of the wing, and if limb mesenchyme is replaced by non-limb mesenchyme beneath AER, the AER regresses. This may demonstrate that:
A. the limb mesenchyme cells induce and sustain AER.
B. the mesenchyme cells specify the type: wing or limb.
C. the AER is responsible for specifying the type: wing or limb.
D. the AER is responsible for sustained outgrowth and development of the limb.
E. the AER does not specify the type: wing or limb.
Which combination of above statements is demonstrated by the experiment?
