Chapter 18- Metamorphosis/regeneration/aging Most animals have a distinct larval stage Massive changes often occur from larval to adult organism transition Larva Adult Aquatic, tail fins Gills Herbivore Excrete ammonia Terrestrial, tail-less, ________ _________ ___________ Excrete __________ Metamorphosis is dictated by _________ T4 In frogs- hormones __________ (T4) and _________________ (T3) are secreted from the ________ T3 Fig. 18.3

Thyroid stimulating hormone A. Metamorphosis (cont.) If remove thyroid from tadpole- …becomes giant _______ The response to hormones is ____________ specific The same stimulus can promote ___________in one tissue and ______________ in another T3 promotes ____________ of tadpole head and body, but cell ___________ in the tail The timing of hormone production is done by 1. The____________ 2. The _________________ (which regulates thyroid hormone production) Thyroid stimulating hormone ___ Hypothalamus _________ _______ _______ _______ ___

A. Metamorphosis (cont.) A. Metamorphosis (cont.) If transplant a second tail- it still degenerates by ________ Fig. 18.5 Transplanted tail tip Transplanted tail tip regresses But if transplant another eye cup, it ________________ How are these events of metamorphosis coordinated?? Need tail until have legs for locomotion Need gills until lung muscles develop One theory- “______________________________” As _____________ levels increase, different events occur If high levels of ________________ -tail regression prior to _________________ development Go to morphogenesis on Vade Mecum

A. Metamorphosis (cont.) A. Metamorphosis (cont.) Fig. 18.7 Mechanism of thyroid hormone effects Pre-metamorphosis Early metamorphosis Metamorphosis _____ T3 ____ T3r T3 T3r ____ T3 ____T3r T3 receptor gene Activate ____________ genes ____T3,T4 ______ T3,T4 _____ T3,T4

3. ___________________ no _____________development A. Metamorphosis (cont.) Heterochrony Definition- The phenomenon whereby animals change the ______________ and ____________________ of characters Usually refers to creatures with _________ phases 1. __________- retention of juvenile form in body but germ cells/gonads mature _______________ 2.___________- retention of juvenile form of body but germ cells and gonads mature ____________________________ 3. ___________________ no _____________development

1. ___________ (Salamander) A. Metamorphosis (cont.) 1. ___________ (Salamander) a. Mexican axolotl- body fails to mature do to lack of __________ from pituitary gland (hence no ___ produced by thyroid gland) If treat axolotl with __________________, develops into creature not seen in nature Normal + __________ Fig. 18.8

1. ______________ (Salamander) Heterochrony 1. ______________ (Salamander) TSH-RF TSH T3, T4 No _______ No _________ No ________

2. _________________ (Salamander) A. Metamorphosis (cont.) 1. Neoteny (Salamander) b. Tigrinum (salamander in Rocky Mtns) stays in larval form if cold Metamorph into land-dwelling creature if _____ Why? Because can’t secrete ________________ ___________ at low temps. c. Other salamanders can’t respond at all to thyroid hormones 2. _________________ (Salamander) a. Occidentalis (tree living salamander) Remains in juvenile phase to retain _____________.

3. ___________ Development A. Metamorphosis (cont.) 3. ___________ Development E. Coqui (frog) – In _____________ only Develops directly into frog (no ____________ stage) Egg is 20X larger than xenopus Early development is similar to other frogs , but ____________ form right after __________ closure Fig. 18.10 Is larval stage only required for creatures with small eggs?? 1998- Noisy problem when introduced into Hawaii- cluster can produce 70-90 decibels (75 decibels leads to hearing loss)

Insect morphogenesis Instead of simply remodeling (e.g. amphibians), insects _______ tissues and ___________ new ones Insects ______ (shed their cuticle) Often go through multiple _________ (larval molts) Each molt generates a ________ organism Most of the previous body is destroyed by _________ _____________ lay dormant until needed to create adult

Recall Fruit Fly development Imaginal discs Fig. 18.12 Imaginal discs lay dormant until needed to create adult

What dictates insect morphogenesis?? Answer: Primarily ________(actually 20-hydroxyecdysone) But, ___________ (JH) levels dictate __________ effect Low Ecdysone Next _______ stage High ___ _______ stage High Ecdysone _______ stage Low ___ High Ecdysone

How does ecdysone work? Ecdysone cannot bind _____ Must first bind the ecdysone _________ Fig. 18.23 The _______________ ______ binds DNA and creates “__________” These puffs contain _________ that are _________ These genes encode _____________________ that promote _____________

B. Regeneration Three types- 1. ________ – e.g. a salamander growing back an entire limb 2. ____________ – the re-patterning of existing tissues, without requiring ____________ e.g. planaria regeneration of head and tail regions 3. _____________ – cells divide but maintain their ____________ phenotype e.g. the mammalian ______- the removed lobe does not grow back, but the remaining _____ compensate by “___________________”

C. Aging Definition- Time-related ______________of the physiological functions necessary for survival and function Some developmental biologists tout that animals are only needed long enough to fill the need of ________________, then die (as occurs in ______ and __________) Maximum life span- the _______________ number of years that a member of a species is known to have lived Life ___________- the age to which __ of the population survives In 1780 England- ___ yrs In 1780 Massachusetts- ___ yrs Today in Afghanistan, Cambodia, etc- ____ yrs Today in America- ___ yrs (male) and __ yrs (female) In 1935 America- ____ yrs (when Social Security was initiated)

2. General ______________- the build up of__________________ B. Aging (cont.) Theories of Aging 1. _____________- reactive oxygen species (ROS) in mitochondria progressively damage DNA, proteins, etc Evidence- Drosophila and C. Elegans liver longer (up to 40%longer) if over-express catalase (which destroys ROS) 2. General ______________- the build up of__________________ Evidence- Species with more efficient DNA repair enzymes tend to live longer Life span 3. _________________ genome damage Leads to decreased ______ __________, increased ROS, and increased ____________ DNA repair efficiency Fig. 18.36

4. ___________ shortening 15.3 15.2 15.1 14 13.3 13.1 12 11 11.1 11.2 13.2 15 21 22 23.1 23.3 31.1 31.2 31.3 32 33.1 33.3 34 35.1 35.3 35.2 33.2 23.2 B. Aging (cont.) Theories of Aging 15.3 15.2 15.1 14 13.3 13.1 12 11 11.1 11.2 13.2 15 21 22 23.1 23.3 31.1 31.2 31.3 32 33.1 33.3 34 35.1 .3 35.2 33.2 23.2 4. ___________ shortening Background- Telomere ends are normally maintained by the enzyme _____________ (not DNA polymerase) Evidence- a) Telomeres shorten as cells divide in culture until cell division stops, and cell division starts again if express telomerase b) Telomerase-deficient mice show profound ________ defects Problem with theory- _________________ between telomere length and life span of different species or even with a species

Fig. 18.37- 8 yr old children with progeria B. Aging (cont.) Fig. 18.37- 8 yr old children with progeria Theories of Aging 5. __________ aging programs Evidence- a) Known “old-age” genetic defects Hutchinson-Gilford _______ syndrome in humans – 1/yr identified in US Disease gene identified- Nature, April 24, 2003;Gordon et al. Leslie Gordon is mother of progeria child C to T transition in LMNA (Lamin A) gene (unknown function) 2) __________ gene mutation in mice b) C. elegans- can extend lives __________ by altering genes involved in larva- to adult genetic pathway