Chapter 15 Part 3: Collective Migration

Question 1

What two processes are required for collective migration

Answer 1

1) contact inhibition to stop movement 2) co attraction between crest cells.

Question 2

neural crest cells that can undergo collective migration are able to undergo two pathways to ensure contact inhibition and co-attraction

Answer 2

1) cells have Wnt (non canonical- planar cell polarity pathway), resulting in RhoA activation and acomyosin contraction 2) cells also have complement3A secretion, which attracts neural crest cells expressing C3A receptors. there is also slight levels of Ncadherin, to enhance the adherence of the population.

Question 3

Two migration pathways of trunk neural crest cells

Answer 3

1) ventral pathway
2) dorsolateral pathway

Question 4

the earliest trunk neural crest cells start migrating using the ___ pathway. What do these cells become?

Answer 4

via the ventral pathway. these cells become dorsal ganglia (sensory) and autonomic neurons, as well as adrenomedullary cells and glial/schwaann cells.

Question 5

Which proteins ensure that the earliest migrating trunk neural crest cells migrate via the ventral pathway?

Answer 5

1. Slit protein
2. condroitan sulphate
3. proteoglycans

they physically block the dorsal pathway, forcing early neural crest cells into a ventral path of migration.

Question 6

trunk cells in the ventral pathway can either move ___ or ___ somites. what do each result in?

Answer 6

between somites or through.

movement between somites results in formation of sympathetic (autonomic) ganglia or the aorta.

movement through the somites is the normal ventral trunk path of migration

Question 7

Ventral moving trunk neural crest cells move between the somites initially, but then this pathway gets blocked by ____ protein that repels neural crest cells, resulting in most neural cress trunk cells to move through the somites.

Answer 7

Ventral moving trunk neural crest cells move between the somites initially, but then this pathway gets blocked by SEMAPHORIN 3F protein that repels neural crest cells, resulting in most neural cress trunk cells to move through the somites.

Question 8

when trunk neural crest cells move ventral through somites, what proteins help them travel through the anterior sclerotomes? What ensures that ventrally-migrating neural crest trunk cells only migrate through the ANTERIOR regions of the sclerotomes?

Answer 8

fibronectin and laminin in the anterior sclerotomes help the trunk neural crest cells migrate through anterior regions. Ephrin in the posterior region of each clerotome prevent crest cells from travelling through this portion, forcing the neural trunk crest cells to only tracel through anterior aspect of scleortomes.

Question 9

what gives the peripheral nervous system a segmented appearance?

Answer 9

fibronectin and laminin in the anterior sclerotomes help the trunk neural crest cells migrate through anterior regions.

Ephrin AND SEMAPHORIN3F BLOCKING PROTEIN in the posterior region of each Sclerotome prevent crest cells from travelling through this portion, forcing the neural trunk crest cells to only tracel through anterior aspect of scleROtomes.

Question 10

in order to innervate the gut, which pathway do neural crest vagal and sacral cells go?

Answer 10

the ventral pathway

Question 12

vagal neural crest cells migrate ventrally past the somites to enter the ___ and spread into the digestive tube, while sacral neural crest cells migrate ventrally past the somites to enter the ____.

Answer 12

vagal neural crest cells migrate ventrally past the somites to enter the foregut and spread into the digestive tube, while sacral neural crest cells migrate ventrally past the somites to enter the hindgut.

Question 13

vagal neural crest cells migrate ventrally past the somites to enter the foregut and spread into the digestive tube, while sacral neural crest cells migrate ventrally past the somites to enter the hindgut.

How do the vagal+sacral neural crest cells get attracted to the digestive tube?

Answer 13

glial-derive neurotropic factor is a paracrine factor that gets produced by the gut mesenchyme, and it binds to neurual crest receptor RET on the surface of the vagal and sacral neural crest cells.

Question 14

___ ____ ___ ___(GDNF) is a paracrine factor that gets produced by the gut mesenchyme, and it binds to neurual crest receptor ____ on the surface of the vagal and sacral neural crest cells.

Answer 14

glial-derive neurotropic factor is a paracrine factor that gets produced by the gut mesenchyme, and it binds to neurual crest receptor RET on the surface of the vagal and sacral neural crest cells.

Question 15

what allows vagal neural crest cells to migrate deeper into the gut?

Answer 15

bagal neural crest cells migrate deeper into the gut compared to sacral neural crest cells because they contain more RET receptors, making them more attracted to GDNF.

Question 16

What happens if you do not have vagal crest cells

Answer 16

would not have good innervation of the gut, resulting in poor perstaltic movement.

Question 17

trunk neural crest cells that migrate dorsalaterally (as opposed to early ventral migration) become. Where do they travel and how do they exert their function?

Answer 17

melanocytes. these NCs travel between epidermis and dermis and enters the ectoderm via the holes in the basal lamina. They will colonize skin and hair follicles once inside the ectoderm.

Question 18

when neural crest cells go through the dorsolateral pathway, they switch between ____ precursors to a ___ precursor due to ___- transcription factor repression. outline the mechanism.

Answer 18

when neural crest cells go through the dorsolateral pathway, they switch between NEURAL/GLIAL precursors to a MELANOBLAST precursor due to FOXD3 ranscription factor.

Foxd3 expression results in MITF repression (a TF required for melanocyte specification). If Foxd3 is not present (what happens in dorsolateral pathway), MITF will be active and will direct cells to 1) produce pigment, 2) travel via dorrsolateral route into skin, 3) become resistant to apoptosis.

If animals are heterozygrous for MITF gene, there will be fewer pigment cells travelling to the center of the body, causing loss of pigment of melanocytes.

Question 19

Dorsolateral pathway:

Foxd3 expression results in____repression (a TF required for melanocyte specification). If Foxd3 is not present (what happens in dorsolateral pathway), ___ will be ___ and will direct cells to: (3 things)

Answer 19

Foxd3 expression results in MITF repression (a TF required for melanocyte specification). If Foxd3 is not present (what happens in dorsolateral pathway), MITF will be active and will direct cells to 1) produce pigment, 2) travel via dorrsolateral route into skin, 3) become resistant to apoptosis.

Question 20

once specified (because of MITF activity), the melanoblasts upregulate ____ and ___ receptors, which allows for cells to readily migrate through the extracellular matrices containing ___ and ___.

the ___ reecptor is also present on melanoblast cells expressing MITF, and binds to STEM CELL FACTOR (SCF) on dermal (surface ectoderm) cells.What does this induce?

Answer 20

once specified (because of MITF activity), the melanoblasts upregulate EPHB2 and EDNRB2 receptors, which allows for cells to readily migrate through the extracellular matrices containing EPHRIN and ENDOTHELIN3.

the KIT reecptor is also present on melanoblast cells expressing MITF, and binds to STEM CELL FACTOR (SCF) on dermal (surface ectoderm) cells.

when kit binds to scf, kit prevents apoptosis and stimulates proliferation of the melanoblast cells migrating via the dorsolateral pathway. Mutations or loss of kit results in incomplete coverage of skin with melanocytes (patchy skin)

Question 21

What do cranial neural crest cells form?

Answer 21

melanocytes, glial cells, peripheral neurons, bones and cartilage and connective tissue in the head.

Question 22

cranial cells migrate (and delaminate) from neural folds of the neural tube before the neural tube is fused together. Subsequent migration of these cells however is directed by:

Answer 22

the underlying segmentation of the hindbrain (recall: the hindbrain is segmented into rhombomeres).

Question 23

the cranial nerual crest cells migrate via ____ pathway from rhombomeres anterior to ____, an into the ____ ___ and the frontonasal process that forms the face.

Answer 23

the cranial nerual crest cells migrate via VENTRAL pathway from region anterior to RHOMBOMERE8, an into the PHARYNGEAL ARCHES and the frontonasal process that forms the face.

Question 24

Neural crest cells from midbrain and rhombomeres 1-2 of hindbrain migrate to the ___ pharyngeal arch. What do they form?

Answer 24

the migrate from R1-2 to the 1st pharyngeal arch. forms jaw, middle ear bones (incus and malleus), trigeminal nerces, ciliary ganglion, and frontonasal processes to form bones of the forehead, bridge of nose and palate.

Question 25

cranial neural crest cells from rhombomere4 migrates to the ___ pharyngeal arch to form:

Answer 25

cranial neural crest cells ventrally migrate from R4 to 2nd pharyngeal arch to form the upper hyoid cartilage, stapes of middle ear, and facial nerve.

Question 26

cranial neural crest cells from rhombomeres 6,7,8 travel to the ___ and __ pharyngeal arches to form:

Answer 26

cranial neural crest cells from rhombomeres 6,7,8 travel to the 3 and 4th pharyngeal arches to form the lower portion of hyoid cartilage, thymus, parathyroid gland, thyroid gland, assists in formation of aorta and pulmonary arteries in the heart.

Question 27

Chase and Run Model of Migration:

normally, the three different streams of cranial neural crest cells are kept separate by chemorepellent nature of _____and ____ and ___ (proteoglycan)

Answer 27

The three different streams of cranial neural crest cells are kept separate by chemorepellent nature of ephrins and semaphorins and versican (proteoglycan)

Question 28

Chase and Run Model of Migration:

ventrally migrating cells follow blacode cells because placodal cells secrete ______, which is a chemoattractant (rather than the chemorepellent ephrin and semaphorin) and binds to ____ receptors on neural crest cells, ALLOWING FOR A CHASE.

-once the neural crest cells reach the placode due to attraction, ___ ____occurs between the neural crest cells and aplcode cells, causing the placode cells to mgirate away from the site of contact (RUN).

Answer 28

ventrally migrating cells follow blacode cells because placodal cells secrete STROMA-DERIVED FACTOR 1 (SDF1), which is a chemoattractant (rather than the chemorepellent ephrin and semaphorin) and binds to CXCR4 receptors on neural crest cells, (CHASE)

-recall that rac1 allows for lamellopodia extension and movement, whereas rhoA is expressed in the opposite end of the cell, and results in actomyosin contraction for regression (allows for directed movement)

once the neural crest cells reach the placode due to attraction, contact inhibition occurs between the neural crest cells and aplcode cells, causing the placode cells to mgirate away from the site of contact (RUN).

• the chemoattractive force of SDF1-CXCR4 interactions will start the chase again in the ventral direction toward the running placode